-
Military Medical Research Jun 2023Choosing the appropriate antipsychotic drug (APD) treatment for patients with schizophrenia (SCZ) can be challenging, as the treatment response to APD is highly variable...
BACKGROUND
Choosing the appropriate antipsychotic drug (APD) treatment for patients with schizophrenia (SCZ) can be challenging, as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers. Previous studies have indicated the association between treatment response and genetic and epigenetic factors, but no effective biomarkers have been identified. Hence, further research is imperative to enhance precision medicine in SCZ treatment.
METHODS
Participants with SCZ were recruited from two randomized trials. The discovery cohort was recruited from the CAPOC trial (n = 2307) involved 6 weeks of treatment and equally randomized the participants to the Olanzapine, Risperidone, Quetiapine, Aripiprazole, Ziprasidone, and Haloperidol/Perphenazine (subsequently equally assigned to one or the other) groups. The external validation cohort was recruited from the CAPEC trial (n = 1379), which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine, Risperidone, and Aripiprazole groups. Additionally, healthy controls (n = 275) from the local community were utilized as a genetic/epigenetic reference. The genetic and epigenetic (DNA methylation) risks of SCZ were assessed using the polygenic risk score (PRS) and polymethylation score, respectively. The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis, methylation quantitative trait loci, colocalization, and promoter-anchored chromatin interaction. Machine learning was used to develop a prediction model for treatment response, which was evaluated for accuracy and clinical benefit using the area under curve (AUC) for classification, R for regression, and decision curve analysis.
RESULTS
Six risk genes for SCZ (LINC01795, DDHD2, SBNO1, KCNG2, SEMA7A, and RUFY1) involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response. The developed and externally validated prediction model, which incorporated clinical information, PRS, genetic risk score (GRS), and proxy methylation level (proxyDNAm), demonstrated positive benefits for a wide range of patients receiving different APDs, regardless of sex [discovery cohort: AUC = 0.874 (95% CI 0.867-0.881), R = 0.478; external validation cohort: AUC = 0.851 (95% CI 0.841-0.861), R = 0.507].
CONCLUSIONS
This study presents a promising precision medicine approach to evaluate treatment response, which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ. Trial registration Chinese Clinical Trial Registry ( https://www.chictr.org.cn/ ), 18. Aug 2009 retrospectively registered: CAPOC-ChiCTR-RNC-09000521 ( https://www.chictr.org.cn/showproj.aspx?proj=9014 ), CAPEC-ChiCTR-RNC-09000522 ( https://www.chictr.org.cn/showproj.aspx?proj=9013 ).
Topics: Humans; Antipsychotic Agents; Schizophrenia; Olanzapine; Risperidone; Aripiprazole; Precision Medicine; Multiomics; Benzodiazepines; Randomized Controlled Trials as Topic; Phospholipases
PubMed: 37269009
DOI: 10.1186/s40779-023-00459-7 -
Neuropsychopharmacology : Official... May 2015Antipsychotic drugs are thought to produce secondary negative symptoms, which can also exacerbate primary negative symptoms. In the present study, we examined whether... (Clinical Trial)
Clinical Trial
Antipsychotic drugs are thought to produce secondary negative symptoms, which can also exacerbate primary negative symptoms. In the present study, we examined whether motivational deficits in particular were related to antipsychotic treatment in patients with schizophrenia in a dose-dependent manner. Five hundred and twenty individuals with schizophrenia who were receiving antipsychotic monotherapy for at least 6 months and followed prospectively were included in the present study. Participants were receiving one of five antipsychotic medications (olanzapine, perphenazine, quetiapine, risperidone, or ziprasidone), and analyses were conducted for patients receiving each drug separately. Analysis of covariance models were constructed to examine the effect of antipsychotic dose on level of motivational impairment, controlling for selected demographic and clinical variables (eg, positive symptoms). Level of motivation, or deficits therein, were evaluated using a derived measure from the Quality of Life Scale, and in addition with scores derived from the Positive and Negative Syndrome Scale. Antipsychotic dose was not related to the level of amotivation for any of the medications examined. Moreover, severity of sedation was not significantly related to the degree of amotivation. One hundred and twenty-one individuals were identified as antipsychotic-free at baseline, and after 6 months of antipsychotic treatment, no change in motivation was found. Chronic treatment with antipsychotics does not necessarily impede or enhance goal-directed motivation in patients with schizophrenia. It is possible that the negative impact of antipsychotics in this regard is overstated; conversely, the present results also indicate that we must look beyond antipsychotics in our efforts to improve motivation.
Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Female; Humans; Hypnotics and Sedatives; Longitudinal Studies; Male; Middle Aged; Motivation; Psychological Tests; Quality of Life; Schizophrenia; Schizophrenic Psychology; United States; Young Adult
PubMed: 25567425
DOI: 10.1038/npp.2015.3 -
The Cochrane Database of Systematic... Mar 2015Perphenazine is an old phenothiazine antipsychotic with a potency similar to haloperidol. It has been used for many years and is popular in the northern European... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Perphenazine is an old phenothiazine antipsychotic with a potency similar to haloperidol. It has been used for many years and is popular in the northern European countries and Japan.
OBJECTIVES
To examine the clinical effects and safety of perphenazine for those with schizophrenia and schizophrenia-like psychoses.
SEARCH METHODS
We updated our original search using the Cochrane Schizophrenia Group's register (September 2013), references of all included studies and contacted pharmaceutical companies and authors of included studies in order to identify further trials.
SELECTION CRITERIA
We included all randomised controlled trials that compared perphenazine with other treatments for people with schizophrenia and/or schizophrenia-like psychoses. We excluded trials of depot formulations of perphenazine.
DATA COLLECTION AND ANALYSIS
Two review authors independently inspected citations and, where possible, abstracts. We ordered papers, inspected and quality assessed them. We extracted data, again working independently. If loss to follow-up was greater than 50% we considered results as 'prone to bias'. For dichotomous data, we calculated risk ratios (RR) and for continuous data we calculated mean differences (MD), both with the 95% confidence intervals (CI). We assessed quality of data using the GRADE (Grading of Recommendations Assessment, Development and Evaluationtool) and assessed risk of bias for included studies.
MAIN RESULTS
Thirty-one studies fulfilled the inclusion criteria, with a total of 4662 participants (of which 4522 were receiving the drugs relevant to our comparison) and presented data that could be used for at least one comparison. The trial centres were located in Europe (especially Scandinavia), Japan and Northern America.When comparing perphenazine with placebo, for our primary outcome of clinical response, results favoured perphenazine with significantly more people receiving placebo rated as either 'no better or deterioration' for global state than people receiving perphenazine (1 RCT, n = 61 RR 0.32 CI 0.13 to 0.78, very low quality evidence). More people receiving placebo relapsed, although not a statistically significant number (1 RCT, n = 48, RR 0.14 CI 0.02 to 1.07, very low quality evidence). Death was not reported in the perphenazine versus placebo comparison. Experiences of dystonia were equivocal between groups (1 RCT, n = 48, RR 1.00 CI 0.07 to 15.08, very low quality evidence); other outcomes not reported in this comparison include serious adverse events, economic outcomes, and service use and hospitalisation.For the comparison of perphenazine versus any other antipsychotic drugs, no real differences in effect between the drugs were found. There was no significant difference between groups for those considered 'no better or deterioration' (17 RCTs, n = 1879, RR 1.04 CI 0.91 to 1.17, very low quality evidence). For mental state outcome of 'no effect' of the study drug, there was again no significant difference between groups (4 RCTs, n = 383, RR 1.24 CI 0.61 to 2.52, very low quality evidence). Death was not reported in any of the included studies. There was no significant difference in rates of dystonia with perphenazine versus any other antipsychotic drugs (4 RCTs, n = 416, RR 1.36 CI 0.23 to 8.16, very low quality evidence), nor was there a significant difference between groups for serious adverse events (2 RCTs, n = 1760, RR 0.98 CI 0.68 to 1.41, very low quality evidence).
AUTHORS' CONCLUSIONS
Although perphenazine has been used in randomised trials for more than 50 years, incomplete reporting and the variety of comparators used make it impossible to draw clear conclusions. All data for the main outcomes in this review were of very low quality evidence. At best we can say that perphenazine showed similar effects and adverse events as several of the other antipsychotic drugs. Since perphenazine is a relatively inexpensive and frequently used compound, further trials are justified to clarify the properties of this classical antipsychotic drug.
Topics: Antipsychotic Agents; Humans; Mental Disorders; Perphenazine; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 25749632
DOI: 10.1002/14651858.CD003443.pub3 -
Cureus Jan 2024Antipsychotics are considered a gold standard treatment for schizophrenia. However, there is considerable variation in antipsychotic medication choice. Factors...
Antipsychotics are considered a gold standard treatment for schizophrenia. However, there is considerable variation in antipsychotic medication choice. Factors considered involved include symptomatology, prior response, and adverse reactions. This case report presents a 38-year-old male patient with schizophrenia in acute psychosis refractory to several antipsychotics. Hypotheses for the mechanism of action of antipsychotics and psychopharmacology are discussed, and treatment resistance is defined. The patient's psychiatric, medical, and social history and past antipsychotic medications are reviewed. Afterward, the rationale for initiating perphenazine is discussed, and the patient's improvement with this medication is examined. Current literature on perphenazine's efficacy is also reviewed and discussed alongside its limitations.
PubMed: 38313962
DOI: 10.7759/cureus.51593 -
Cell Apr 2020Protein phosphatase 2A (PP2A) enzymes can suppress tumors, but they are often inactivated in human cancers overexpressing inhibitory proteins. Here, we identify a class...
Protein phosphatase 2A (PP2A) enzymes can suppress tumors, but they are often inactivated in human cancers overexpressing inhibitory proteins. Here, we identify a class of small-molecule iHAPs (improved heterocyclic activators of PP2A) that kill leukemia cells by allosterically assembling a specific heterotrimeric PP2A holoenzyme consisting of PPP2R1A (scaffold), PPP2R5E (B56ε, regulatory), and PPP2CA (catalytic) subunits. One compound, iHAP1, activates this complex but does not inhibit dopamine receptor D2, a mediator of neurologic toxicity induced by perphenazine and related neuroleptics. The PP2A complex activated by iHAP1 dephosphorylates the MYBL2 transcription factor on Ser241, causing irreversible arrest of leukemia and other cancer cells in prometaphase. In contrast, SMAPs, a separate class of compounds, activate PP2A holoenzymes containing a different regulatory subunit, do not dephosphorylate MYBL2, and arrest tumor cells in G1 phase. Our findings demonstrate that small molecules can serve as allosteric switches to activate distinct PP2A complexes with unique substrates.
Topics: Apoptosis; Cell Cycle Proteins; Cell Line, Tumor; Enzyme Activators; G1 Phase; Humans; Multiprotein Complexes; Phenothiazines; Phosphorylation; Protein Phosphatase 2; Protein Subunits; Trans-Activators; Transcription Factors
PubMed: 32315619
DOI: 10.1016/j.cell.2020.03.051 -
The Cochrane Database of Systematic... Apr 2005Benperidol is a relatively old antipsychotic drug that has been marketed since 1966. It has been used in Germany for 30 years, but is also available in Belgium, Greece,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Benperidol is a relatively old antipsychotic drug that has been marketed since 1966. It has been used in Germany for 30 years, but is also available in Belgium, Greece, Italy, the Netherlands and the UK. Benperidol is a butyrophenone antipsychotic, with the highest neuroleptic potency in terms of D2 receptor blockade. Those taking it are therefore reputed to be at high risk of extrapyramidal side effects, but benperidol's unusual profile may render it valuable to subgroups of people with schizophrenia.
OBJECTIVES
To examine the clinical effects and safety of benperidol for those with schizophrenia and schizophrenia-like psychoses.
SEARCH STRATEGY
We searched the Cochrane Schizophrenia Group's register (November 2004) for this update.
SELECTION CRITERIA
We included all randomised controlled trials that compared benperidol with other treatments for people with schizophrenia, or schizophrenia-like psychoses.
DATA COLLECTION AND ANALYSIS
We reliably selected studies, quality rated them and extracted data. We independently extracted data but excluded data if loss to follow up was greater than 50%. For dichotomous data, we estimated relative risks (RR), with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat/harm statistic (NNT/H) and used intention-to-treat analysis.
MAIN RESULTS
The update yielded no further studies for inclusion in the review. We identified only one unpublished poorly randomised controlled trial (N=40, duration 30 days, comparison perphenazine). Although benperidol was inferior to perphenazine (1 RCT, N=40, global state no better or worse RR 8.0 CI 2.1 to 30, NNH 1.4 CI 1 to 2) poor reporting suggests that an overestimate of effect is likely. It was not possible to report other outcomes.
AUTHORS' CONCLUSIONS
Currently, there are insufficient data from randomised trials to assess the clinical effects of benperidol. This compound merits further research interest.
Topics: Antipsychotic Agents; Benperidol; Humans; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 15846648
DOI: 10.1002/14651858.CD003083.pub2 -
The Cochrane Database of Systematic... May 2014Many people with schizophrenia do not achieve a satisfactory treatment response with just antipsychotic drug treatment and various adjunct medications are used to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Many people with schizophrenia do not achieve a satisfactory treatment response with just antipsychotic drug treatment and various adjunct medications are used to promote additional response. The antiepileptic carbamazepine is one such drug.
OBJECTIVES
To examine whether carbamazepine or oxcarbazepine alone is an effective treatment for schizophrenia and schizoaffective psychoses and whether carbamazepine or oxcarbazepine augmentation of neuroleptic medication is an effective treatment for the same illnesses.
SEARCH METHODS
For the original version we searched The Cochrane Schizophrenia Group's Register of Trials (December 2001), The Cochrane Library (Issue 3, 2001), MEDLINE (1966-2001), EMBASE (1980-2001), Biological Abstracts (1980-2001), PsycLIT (1886-2001) and PSYNDEX (1974-2001). For the most recent update we searched the Cochrane Schizophrenia Group's Register of Trials in July 2012. We also inspected references of all identified studies for further trials and contacted relevant pharmaceutical companies and authors for additional data.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) comparing carbamazepine or compounds of the carbamazepine family with placebo or no intervention, whether as sole treatment or as an adjunct to antipsychotic medication for the treatment of schizophrenia and/or schizoaffective psychoses.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For homogenous dichotomous data we calculated fixed-effect, risk ratio (RR), with 95% confidence intervals (CIs) on an intention-to-treat basis. For continuous data, we calculated mean differences (MD). We assessed the risk of bias for included studies and created a 'Summary of findings' table using GRADE.
MAIN RESULTS
The updated search did not reveal any further studies that met our inclusion criteria. The number of included studies therefore remains at 10 with the number of participants randomised still 283.One study comparing carbamazepine with placebo as the sole treatment for schizophrenia was abandoned early due to high relapse rate with 26 out of 31 participants relapsing by three months. No effect of carbamazepine was evident with no difference in relapse between the two groups (1 RCT n = 31, RR 1.07 CI 0.78 to 1.45). Another study compared carbamazepine with antipsychotics as the sole treatment for schizophrenia. No differences in terms of mental state were found when comparing 50% reduction in Brief Psychiatric Rating Scale (BPRS) scores (1 RCT n = 38, RR 1.23 CI 0.78 to 1.92). A favourable effect for carbamazepine was found when more people who received the antipsychotic (perphenazine) had parkinsonism (1 RCT n = 38, RR 0.03 CI 0.00 to 0.043). Eight studies compared adjunctive carbamazepine versus adjunctive placebo, we were able use GRADE for quality of evidence for these results. Adding carbamazepine to antipsychotic treatment was as acceptable as adding placebo with no difference between the numbers leaving the study early from each group (8 RCTs n = 182, RR 0.47 CI 0.16 to 1.35, very low quality evidence). Carbamazepine augmentation was superior compared with antipsychotics alone in terms of overall global improvement, but participant numbers were low (2 RCTs n = 38, RR 0.57 CI 0.37 to 0.88). There were no differences for the mental state outcome of 50% reduction in BPRS scores (6 RCTs n = 147, RR 0.86 CI 0.67 to 1.12, low quality evidence). Less people in the carbamazepine augmentation group had movement disorders than those taking haloperidol alone (1 RCT n = 20, RR 0.38 CI 0.14 to 1.02). No data were available for the effects of carbamazepine on subgroups of people with schizophrenia and aggressive behaviour, negative symptoms or EEG abnormalities or with schizoaffective disorder.
AUTHORS' CONCLUSIONS
Based on currently available randomised trial-derived evidence, carbamazepine cannot be recommended for routine clinical use for treatment or augmentation of antipsychotic treatment of schizophrenia. At present large, simple well-designed and reported trials are justified - especially if focusing on people with violent episodes and people with schizoaffective disorders or those with both schizophrenia and EEG abnormalities.
Topics: Antimanic Agents; Antipsychotic Agents; Carbamazepine; Combined Modality Therapy; Humans; Randomized Controlled Trials as Topic; Recurrence; Schizophrenia
PubMed: 24789267
DOI: 10.1002/14651858.CD001258.pub3 -
The Cochrane Database of Systematic... Jul 2005Antipsychotic drugs are usually given orally but compliance with medication given by this route may be difficult to quantify. The development of depot injections in the... (Review)
Review
BACKGROUND
Antipsychotic drugs are usually given orally but compliance with medication given by this route may be difficult to quantify. The development of depot injections in the 1960s gave rise to extensive use of depots as a means of long-term maintenance treatment. Perphenazine decanoate and enanthate are depot antipsychotics that belong to the phenothiazine family and have a piperazine ethanol side chain.
OBJECTIVES
To assess the effects of depot perphenazine decanoate and enanthate versus placebo, oral antipsychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes.
SEARCH STRATEGY
We updated previous searches of the Cochrane Schizophrenia Group Register (June 1998), Biological Abstracts (1982-1998), the Cochrane Library (Issue 2, 1998), EMBASE (1980-1998), MEDLINE (1966-1998), and PsycLIT (1974-1998) by searching the Cochrane Schizophrenia Group Register (March 2004). References of all identified trials were also inspected for more studies and industry contacted.
SELECTION CRITERIA
We compared randomised clinical trials focusing on people with schizophrenia where depot perphenazine decanoate and enanthate, oral antipsychotics or other depot preparations.
DATA COLLECTION AND ANALYSIS
We reliably selected studies, quality rated them and extracted data. For dichotomous data we estimated the Relative Risk (RR) with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat statistic (NNT). Analysis was by intention-to-treat.
MAIN RESULTS
Only four studies (Ahlfors 1980, Eufe 1979, Knudsen 1985c, Tegeler 1979), randomising a total 313 people could be included in this review and this combined with an overall lack of usable data limits any interpretation of results. Perphenazine enanthate was not significantly any better or worse than other depot antipsychotics in most of the main outcomes such as global state, relapse or leaving the study early. We found some differences favouring the control groups for adverse effects. One study (Ahlfors 1980) of six months' duration (n=172), compared perphenazine enanthate to clopenthixol decanoate. There were no differences between the two groups for outcomes of global improvement, relapse and leaving the study early. More people in the perphenazine enanthate group, however, required anticholinergic drugs than those allocated to clopenthixol decanoate (RR 1.12 CI 1.0 to 1.2, NNT 10).A single study (n=64, duration six weeks) compared perphenazine enanthate and its longer acting decanoate ester. Data on relapse and leaving the study early failed to show convincing differences. The enanthate group, however, experienced more movement disorders (RR 1.36, CI 1.1 to 1.8 NNT 5) than those allocated the decanoate ester of the same drug and required more anticholinergic drugs (RR 1.47 CI 1.1 to 2.0, NNT 4).
AUTHORS' CONCLUSIONS
Depot perphenazine is in clinical use in the Nordic countries, Belgium, Portugal and the Netherlands. At a conservative estimate, a quarter of a million people suffer from schizophrenia in those countries and could be treated with depot perphenazine. The total number of participants in the four trials with useful data is 313. None of the studies observed the effects of oral versus depot antipsychotic drugs. Until well conducted and reported randomised trials are undertaken clinicians will be in doubt as to the effects of perphenazine depots and people with schizophrenia should exercise their own judgement or ask to be randomised.
Topics: Antipsychotic Agents; Delayed-Action Preparations; Humans; Perphenazine; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 16034865
DOI: 10.1002/14651858.CD001717.pub2 -
Journal of B.U.ON. : Official Journal... 2020In the effort to improve treatment effectiveness in glioblastoma, this short note reviewed collected data on the pathophysiology of glioblastoma with particular... (Review)
Review
In the effort to improve treatment effectiveness in glioblastoma, this short note reviewed collected data on the pathophysiology of glioblastoma with particular reference to intersections with the pharmacology of perphenazine. That study identified five areas of potentially beneficial intersection. Data showed seemingly 5 independent perphenazine attributes of benefit to glioblastoma treatment - i) blocking dopamine receptor 2, ii) reducing centrifugal migration of subventricular zone cells by blocking dopamine receptor 3, iii) blocking serotonin receptor 7, iv) activation of protein phosphatase 2, and v) nausea reduction. Perphenazine is fully compatible with current chemoirradiation protocols and with the commonly used ancillary medicines used in clinical practice during the course of glioblastoma. All these attributes argue for a trial of perphenazine's addition to current standard treatment with temozolomide and irradiation. The subventricular zone seeds the brain with mutated cells that become recurrent glioblastoma after centrifugal migration. The current paper shows how perphenazine might reduce that contribution. Perphenazine is an old, generic, cheap, phenothiazine antipsychotic drug that has been in continuous clinical use worldwide since the 1950's. Clinical experience and research data over these decades have shown perphenazine to be well-tolerated in psychiatric populations, in normals, and in non-psychiatric, medically ill populations for whom perphenazine is used to reduce nausea. For now (Summer, 2020) the nature of glioblastoma requires a polypharmacy approach until/unless a core feature and means to address it can be identified in the future. Conclusions: Perphenazine possesses a remarkable constellation of attributes that recommend its use in GB treatment.
Topics: Dopamine Antagonists; Glioblastoma; Humans; Perphenazine
PubMed: 33099901
DOI: No ID Found -
Oncology Letters Jun 2022Glioblastoma multiforme is the most frequent type of malignant brain tumor, and is one of the most lethal and untreatable human tumors with a very poor survival rate....
Perphenazine and prochlorperazine decrease glioblastoma U-87 MG cell migration and invasion: Analysis of the ABCB1 and ABCG2 transporters, E-cadherin, α-tubulin and integrins (α3, α5, and β1) levels.
Glioblastoma multiforme is the most frequent type of malignant brain tumor, and is one of the most lethal and untreatable human tumors with a very poor survival rate. Therefore, novel and effective strategies of treatment are required. Integrins play a crucial role in the regulation of cellular adhesion and invasion. Integrins and α-tubulin are very important in cell migration, whereas E-cadherin plays a main role in tumor metastasis. Notably, drugs serve a crucial role in glioblastoma treatment; however, they have to penetrate the blood-brain barrier (BBB) to be effective. ABC transporters, including ATP binding cassette subfamily B member 1 (ABCB1) and ATP binding cassette subfamily G member 2 (ABCG2), are localized in the brain endothelial capillaries of the BBB, have a crucial role in the development of multidrug resistance and are modulated by phenothiazine derivatives. The impact of perphenazine and prochlorperazine on the motility of human Uppsala 87 malignant glioma (U87-MG) cells was evaluated using a wound-healing assay, cellular migration and invasion were assessed by Transwell assay, and the protein expression levels of ABCB1, ABCG2, E-cadherin, α-tubulin and integrins were determined by western blotting. The present study explored the effects of perphenazine and prochlorperazine on the levels of ABCB1, ABCG2, E-cadherin, α-tubulin and integrins (α3, α5, and β1), as well as on the migratory and invasive ability of U87-MG cells. The results suggested that perphenazine and prochlorperazine may modulate the expression levels of multidrug resistance proteins (they decreased ABCB1 and increased ABCG2 expression), E-cadherin, α-tubulin and integrins, and could impair the migration and invasion of U-87 MG cells. In conclusion, the decrease in migratory and invasive ability following treatment with phenothiazine derivatives due to the increase in ABCG2 and E-cadherin expression, and decrease in α-tubulin and integrins expression, may suggest that research on perphenazine and prochlorperazine in the treatment of glioblastoma is worth continuing.
PubMed: 35527777
DOI: 10.3892/ol.2022.13302