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Cell Death & Disease Feb 2019Pyroptosis, a form of programmed cell death (PCD), has garnered increasing attention as it relates to innate immunity and diseases. However, the involvement of...
Pyroptosis, a form of programmed cell death (PCD), has garnered increasing attention as it relates to innate immunity and diseases. However, the involvement of pyroptosis in the mechanism by which lobaplatin acts against colorectal cancer (CRC) is unclear. Our study revealed that treatment with lobaplatin reduced the viability of HT-29 and HCT116 cells in a dose-dependent manner. Morphologically, HT-29 and HCT116 cells treated with lobaplatin exhibited microscopic features of cell swelling and large bubbles emerging from the plasma membrane, and transmission electron microscopy (TEM) revealed multiple pores in the membrane. GSDME, rather than GSDMD, was cleaved in lobaplatin-induced pyroptosis in HT-29 and HCT116 cells due to caspase-3 activation. Knocking out GSDME switched lobaplatin-induced cell death from pyroptosis to apoptosis but did not affect lobaplatin-mediated inhibition of growth and tumour formation of HT-29 and HCT116 cells in vivo and in vitro. Further investigation indicates that lobaplatin induced reactive oxygen species (ROS) elevation and JNK phosphorylation. NAC, a ROS scavenger, completely reversed the pyroptosis of lobaplatin-treated HT-29 and HCT116 and JNK phosphorylation. Activated JNK recruited Bax to mitochondria, and thereby stimulated cytochrome c release to cytosol, followed by caspase-3/-9 cleavage and pyroptosis induction. Therefore, in colon cancer cells, GSDME mediates lobaplatin-induced pyroptosis downstream of the ROS/JNK/Bax-mitochondrial apoptotic pathway and caspase-3/-9 activation. Our study indicated that GSDME-dependent pyroptosis is an unrecognized mechanism by which lobaplatin eradicates neoplastic cells, which may have important implications for the clinical application of anticancer therapeutics.
Topics: Animals; Antineoplastic Agents; Apoptosis; Caco-2 Cells; Caspase 3; Cell Survival; Colonic Neoplasms; Cyclobutanes; Cytochromes c; HCT116 Cells; HT29 Cells; Humans; Intracellular Signaling Peptides and Proteins; MAP Kinase Kinase 4; Mice; Mice, Inbred BALB C; Mice, Nude; Mitochondria; Organoplatinum Compounds; Phosphate-Binding Proteins; Pyroptosis; RNA, Small Interfering; Reactive Oxygen Species; Receptors, Estrogen; Signal Transduction; Transplantation, Heterologous; bcl-2-Associated X Protein
PubMed: 30804337
DOI: 10.1038/s41419-019-1441-4 -
International Journal of Oncology Sep 2020Retinoblastoma (RB) is one of the most aggressive malignancies affecting infants and children. Platinum drugs are commonly used in the treatment of RB; however, their... (Comparative Study)
Comparative Study
Retinoblastoma (RB) is one of the most aggressive malignancies affecting infants and children. Platinum drugs are commonly used in the treatment of RB; however, their efficacy is often compromised by drug resistance and severe toxicity. The present study aimed to investigate and compare the toxicity and antitumor activity of the third‑generation platinum drugs, carboplatin and lobaplatin, in vitro and in vivo. The Y79 RB cell line was treated with carboplatin or lobaplatin in vitro and then used to establish xenografts in immunodeficient nude mice in vivo; the effects of pharmacological doses of these drugs were then assessed. High concentrations of carboplatin and lobaplatin markedly inhibited Y79 RB cell proliferation in vitro. In addition, the lobaplatin group exhibited higher proportions of early‑stage apoptotic cells than the carboplatin group, while no significant differences in the proportions of cells in the S phase were observed between the 2 groups, as shown by flow cytometry. Significant changes in the E2F1/Cdc25a/Cdk2 pathway in the RB cells were detected by RNA‑seq following carboplatin or lobaplatin intervention. RT‑qPCR, immunofluorescence and immunohistochemical analyses in vivo and in vitro demonstrated that the trends of drug‑induced inhibition of tumor pathological changes may have been regulated through the E2F1/Cdc25a/Cdk2 pathway, and that lobaplatin was more effective than carboplatin in controlling tumors in vivo. On the whole, the findings of the present study demonstrate that lobaplatin is associated with lower cytotoxicity and exerts more prominent therapeutic effects than carboplatin on Y79 RB cells in vitro and in mice in vivo.
Topics: Animals; Antineoplastic Agents; Apoptosis; Carboplatin; Cell Cycle; Cell Line, Tumor; Cyclin-Dependent Kinase 2; Cyclobutanes; E2F1 Transcription Factor; Gene Expression Regulation, Neoplastic; Humans; Mice, Inbred BALB C; Organoplatinum Compounds; Retinal Neoplasms; Retinoblastoma; Xenograft Model Antitumor Assays; cdc25 Phosphatases
PubMed: 32582992
DOI: 10.3892/ijo.2020.5085 -
Medicine Dec 2022Few studies directly compare efficacy and toxicity among lobaplatin, nedaplatin and cisplatin concurrently with intensity-modulated radiotherapy (IMRT) in nasopharyngeal...
Few studies directly compare efficacy and toxicity among lobaplatin, nedaplatin and cisplatin concurrently with intensity-modulated radiotherapy (IMRT) in nasopharyngeal carcinoma (NPC). Totally 141 treatment-naïve NPC without distant metastasis receiving IMRT concurrent with cisplatin or nedaplatin or lobaplatin were retrospectively enrolled. Their response rate, toxicity and long-term survival were compared. Complete response (CR) rates of concurrent lobaplatin (CR-nasopharynx [CR-nx], 82.7%; CR-cervical lymph node [CR-nd], 94.2%) were lower than those of cisplatin (CR-nx, 89.3%; CR-nd, 98.2%) and nedaplatin (CR-nx, 93.9%; CR-nd, 97.0%), but statistical significance wasn't detected. Estimated five-year overall survival (OS), local relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and progression-free survival (PFS) weren't statistically significant between three groups. Multivariable analysis by COX proportional hazards model showed concurrent chemotherapy regimen wasn't an independent prognostic factor. Gastrointestinal toxicity was prevalent in platinum-based concurrent chemotherapy; cisplatin group suffered heavier (≥grade 2) than other two groups. More nephrotoxicity happened in cisplatin group (17.9%) than nedaplatin (9.1%) and lobaplatin (2.0%) groups. Incidence of dermatitis of ≥grade 2 was higher in cisplatin group (60.7%) than nedaplatin (27.3%) and lobaplatin (9.6%) groups. More patients in lobaplatin and nedaplatin groups suffered from any grade thrombocytopenia (P < .001), but incidence of severe thrombocytopenia (≥grade 3) was similar. Economic cost was significant less in lobaplatin group. Cisplatin, nedaplatin and lobaplatin are equally effective when used concurrently with IMRT in NPC. Lobaplatin and nedaplatin have potential to be alternatives to cisplatin in terms of less severe acute side-effects and economic cost.
Topics: Humans; Nasopharyngeal Carcinoma; Cisplatin; Carcinoma; Retrospective Studies; Nasopharyngeal Neoplasms; Chemoradiotherapy; Thrombocytopenia; Antineoplastic Combined Chemotherapy Protocols; Radiotherapy, Intensity-Modulated; Neoplasm Staging; Disease-Free Survival
PubMed: 36626436
DOI: 10.1097/MD.0000000000031187 -
Annals of Translational Medicine Jul 2021This study sought to examine the efficacy and adverse reactions of capecitabine and lobaplatin in the treatment of metastatic human epidermal growth factor receptor 2...
BACKGROUND
This study sought to examine the efficacy and adverse reactions of capecitabine and lobaplatin in the treatment of metastatic human epidermal growth factor receptor 2 (HER-2) negative breast cancer (BC).
METHODS
This retrospective study examined 45 patients diagnosed with advanced HER-2 negative BC. Patients were enrolled in this study from November 2015 to June 2019. The patients received capecitabine and lobaplatin combination therapy. The therapeutic efficacy and side effects were evaluated after at least 2 cycles of treatment.
RESULTS
Therapeutic efficacy and adverse reactions were evaluated in 38 patients, comprising 12 cases of partial response (PR), 19 cases of stable disease (SD), and 7 cases of progressive disease (PD). Among these, 3 patients required treatment delays or dose reductions for subsequent cycles, and 2 patients discontinued treatment. The overall response rate (ORR) was 31.58% and the disease control rate (DCR) was 81.58%. The ORR and DCR for hormone receptor positive, HER-2 negative (HR+/HER-2-) and triple negative breast cancer (TNBC) patients were 31.82% and 31.25%, and 86.36% and 75%, respectively. The median progression free survival (PFS) was 8 months, 6 months, and 6 months in patients receiving the therapeutics as a first-line, second-line, or third-line and beyond treatment, respectively. The main side effects were myelosuppression, including granulocytopenia, thrombocytopenia, and anemia. Among patients with grade 1 side effects or above, 28 patients (73.68%) had myelosuppression, and 13 patients (34.21%) had gastrointestinal reactions. Further, we investigated the association between side effects and clinical outcomes, and found that PFS was increased in patients with myelosuppression and gastrointestinal reactions.
CONCLUSIONS
Capecitabine and lobaplatin combination therapy was effective and well tolerated among patients with advanced HER-2 negative BC.
PubMed: 34430592
DOI: 10.21037/atm-21-2702 -
Frontiers in Oncology 2021Cisplatin-based concurrent chemoradiotherapy is standard of care for locally advanced head and neck cancers (LAHNC). Nedaplatin, lobaplatin and nimotuzumab have shown...
BACKGROUND
Cisplatin-based concurrent chemoradiotherapy is standard of care for locally advanced head and neck cancers (LAHNC). Nedaplatin, lobaplatin and nimotuzumab have shown anti-cancer effect with less gastrointestinal toxicity and nephrotoxicity. However, the profile of hematological toxicities of these agents in combination with radiotherapy has not been fully illustrated.
METHODS
We retrospectively collected the clinical data of consecutive LAHNC patients treated by cisplatin-, nedaplatin-, lobaplatin-, and nimotuzumab-based concurrent chemoradiotherapy. Routine blood cell counts were obtained every 4 to 7 days. Hematological toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
RESULTS
A total of 181 eligible LAHNC patients were assigned to nimotuzumab group (n = 34), cisplatin group (n = 52), nedaplatin group (n = 62) or lobaplatin group (n = 33). Among the four groups, nimotuzumab group displayed lightest hematological toxicities, followed by cisplatin group, nedaplatin group, and lobaplatin group. Lobaplatin was more likely to produce grade 3/4 leukopenia compared with cisplatin (48.5% 25.0%). Compared with cisplatin, nedaplatin and lobaplatin were more likely to cause grade 3/4 thrombocytopenia (nedaplatin 19.4% cisplatin 3.8%; lobaplatin 30.3% cisplatin 3.8%). Similarly, nimotuzumab group showed highest nadir levels among the four groups, followed by cisplatin, nedaplatin, and lobaplatin group. Moreover, concurrent platinum treatment and induction chemotherapy were risk factors of developing grade 3/4 hematological toxicities.
CONCLUSION
Nimotuzumab-based concurrent chemoradiotherapy in head and neck cancers produced the lightest hematological toxicities, followed by cisplatin, nedaplatin, and lobaplatin. Patients should be given specific attention during concurrent chemoradiotherapy, particularly in the presence of previous induction chemotherapy.
PubMed: 34746003
DOI: 10.3389/fonc.2021.762366 -
Dose-response : a Publication of... 2019Lobaplatin is a diastereometric mixture of platinum (II) complexes, which contain a 1,2-bis (aminomethyl) cyclobutane stable ligand and lactic acid. Previous studies...
Lobaplatin is a diastereometric mixture of platinum (II) complexes, which contain a 1,2-bis (aminomethyl) cyclobutane stable ligand and lactic acid. Previous studies have showed that lobaplatin plays inhibiting roles in various types of tumors. However, the role of lobaplatin in prostate cancer remains unknown. Cell viability was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Cell proliferation was detected by cell colony formation assay. Cell migration and invasion were determined by transwell migration and invasion assay. Cell apoptosis was detected by flow cytometry. The messenger RNA and protein expression levels were detected by quantitative real-time polymerase chain reaction and Western blot. Lobaplatin treatment inhibits cell viability, cell proliferation, cell migration, and invasion, while promotes cell apoptosis of prostate cancer cell lines DU145 and PC3. Meanwhile, lobaplatin treatment regulates apoptosis by downregulation of BCL2 expression and upregulation of BAX expression levels. Our study suggests lobaplatin inhibits prostate cancer proliferation and migration through regulation of BCL2 and BAX expression.
PubMed: 31217754
DOI: 10.1177/1559325819850981 -
Frontiers in Oncology 2021Lobaplatin is a third-generation platinum-based antineoplastic agent and is widely used for osteosarcoma treatment before and after tumor removal. However, treatment...
Lobaplatin is a third-generation platinum-based antineoplastic agent and is widely used for osteosarcoma treatment before and after tumor removal. However, treatment failure often results from lobaplatin drug resistance. In our study, we found that SaOS-2 and SOSP-9607 osteosarcoma cells became less sensitive to lobaplatin after treatment with exogenous interleukin (IL)-6. Quantitative proteomic analysis was performed to elucidate the underlying mechanism in SaOS-2 osteosarcoma cells. Cells were divided into a control group (CG), a lobaplatin treatment group (LG), a recombinant human IL-6 (rhIL-6), and a lobaplatin treatment group (rhILG). We performed three biological replicates in each group to compare the differential protein expression between groups using a tandem mass tag (TMT) labeling technology based on liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 1,313 proteins with significant differential expression was identified and quantified. The general characteristics of the significantly enriched proteins were identified by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and protein-protein interaction (PPI) analysis was conducted using IntAct and STRING. In total, 31 proteins were further verified by parallel reaction monitoring (PRM), among which ras GTPase-activating protein-binding protein 1 (G3BP1), fragile X mental retardation syndrome-related protein 1 (hFXR1p), and far upstream element-binding protein 1 (FUBP1) were significantly differentially expressed. Immunohistochemistry results showed that these three proteins are highly expressed in specimens from platinum-resistant osteosarcoma patients, while the proteins are negatively or weakly expressed in specimens from platinum-sensitive osteosarcoma patients. The immunofluorescence staining results were in accord with the immunohistochemistry staining results. siRNA knockdown of FUBP1 showed a strikingly decreased IC50 value for lobaplatin in FUBP1-silenced cells, which verified the role of FUBP1 in the drug susceptibility of osteosarcoma and the potential therapeutic value for increasing the sensitivity to lobaplatin. This is the first proteomic study on a rhIL-6 intervention before lobaplatin treatment in osteosarcoma cells.
PubMed: 33791202
DOI: 10.3389/fonc.2021.602712 -
Medicine Oct 2022Lobaplatin is a new platinum-based cytotoxic chemotherapeutic agent. Endostar is an endogenous angiogenic inhibitor with implicated anti-tumor activity. This study was... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Lobaplatin is a new platinum-based cytotoxic chemotherapeutic agent. Endostar is an endogenous angiogenic inhibitor with implicated anti-tumor activity. This study was to investigate the efficacy and safety of thoracic perfusion of lobaplatin combined with endostar in the treatment of malignant pleural effusions (MPE).
METHODS
We searched the databases of Pubmed, the Cochrane Library, Embase, WanFang Data, and CNKI to select the studies regarding the efficacy and safety of lobaplatin combined with endostar to treat MPE. A total of 10[3-12] randomized controlled trials with 651 patients were included.
RESULTS
The objective response rate (P < .001, odds ratio = 4.08) and disease control rate (P < .001, odds ratio = 3.69) of lobaplatin combined with endostar were significantly higher than lobaplatin alone. In addition, lobaplatin combined with endostar remarkably promoted the quality of life of patients (P < .001, odds ratio = 3.93) compared with lobaplatin alone. Lobaplatin combined with endostar also promoted the quality of life of patients (P < .05, odds ratio = 2.56) compared with cisplatin combined with endostar. At the same time, the leukopenia rate (P < .05, odds ratio = .40) and the incidence of nausea and vomiting (P < .05, odds ratio = .38) of lobaplatin combined with endostar were significantly lower than that of cisplatin combined with endostar.
CONCLUSIONS
The efficacy of lobaplatin combined with endostar was superior to lobaplatin alone. The safety was higher than cisplatin combined with endostar through thoracic perfusion in treating MPE, which indicated that lobaplatin combined with endostar could be the effective agent for controlling MPE.
Topics: Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cyclobutanes; Endostatins; Humans; Organoplatinum Compounds; Perfusion; Pleural Effusion, Malignant; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins
PubMed: 36221355
DOI: 10.1097/MD.0000000000030749 -
Anti-cancer Agents in Medicinal... 2023To investigate the safety and efficacy of lobaplatin-TACE in treating primary hepatocellular carcinoma.
PURPOSE
To investigate the safety and efficacy of lobaplatin-TACE in treating primary hepatocellular carcinoma.
METHODS
The data of 536 patients who underwent TACE in the interventional department from January 2016 to January 2020 were collected. Patients were divided into two groups according to the chemotherapeutic drugs used in TACE.: the epirubicin-TACE group (N = 260) and the lobaplatin-TACE group (N = 276). Primary study endpoint: (1) The tumor response after TACE; (2) The survival rates; Secondary study endpoints:(1) Changes in liver function and blood routine before and after TACE; (2) Occurrence of the post-embolization syndrome and infection after TACE.
RESULTS
The ORR was 35.0% in the epirubicin-TACE group and 51.1% in the lobaplatin-TACE group (p=0.001). The DCR was 73.1% in the epirubicin-TACE group and 82.2% in the lobaplatin-TACE group (p=0.011). The 6-month, 9- month, 12-month, and 15-month survival rates were higher in the lobaplatin-TACE group than in the epirubicin-TACE group (p=0.029, p=0.001, p=0.005, p=0.002). mOS: Epirubicin-TACE group,14.8 months; Lobaplatin-TACE group,18.6 months (p=0.007). mPFS: Epirubicin-TACE group,9.5 months; Lobaplatin-TACE group,12.8 months (P =0.000). There was no statistical difference in ALT, AST, total bilirubin and Leucocyte after TACE between the two groups (p=0.343, p=0.368, p=0.288, p=0.359). The platelet decrease after TACE was more significant in the lobaplatin- TACE group than in the epirubicin-TACE group (p=0.046). There was no statistical difference in the incidence rate of abdominal pain, fever and infection after TACE between the two groups (p=0.502, p=0.602, p=0.726). The incidence of vomiting after TACE in the lobaplatin-TACE group was higher than that in the epirubicin-TACE group (p=0.003).
CONCLUSION
Lobaplatin-TACE has a higher tumor response rate and survival rate. Lobaplatin-TACE is a safe and effective treatment strategy; it is worthy of clinical application.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Epirubicin; Retrospective Studies; Chemoembolization, Therapeutic; Treatment Outcome
PubMed: 35652401
DOI: 10.2174/1871520622666220601115458 -
Drug Design, Development and Therapy 2018Lobaplatin shows antitumor activity against a wide range of tumors, including metastatic breast cancer (BCa). The overexpression of metadherin (MTDH) is associated with...
OBJECTIVE
Lobaplatin shows antitumor activity against a wide range of tumors, including metastatic breast cancer (BCa). The overexpression of metadherin (MTDH) is associated with poor prognosis of BCa patients. This study was designed to investigate the effect of lobaplatin on MCF-7 cell proliferation and its association with MTDH expression.
PATIENTS AND METHODS
Clinical treatment for BCa using lobaplatin, in combination with other general chemotherapy drugs, was administered to 32 BCa patients. The safety, effectiveness, and prognosis in lobaplatin-treated BCa patients were compared with those in controls (n=32). In vitro experiments were performed in MCF-7 cells to investigate the effect of lobaplatin on cell proliferation, apoptosis, and MTDH expression.
RESULTS
We found the intraoperative local chemotherapy using lobaplatin was safe and effective for BCa treatment, in comparison with the patients administered general chemotherapy drugs. Treatment of MCF-7 cell cultures with lobaplatin significantly reduced cell proliferation and increased cell apoptotic percentage. The expression of MTDH and Bcl-2 was inhibited by lobaplatin and that of Bax was increased by lobaplatin. Moreover, we observed the inhibition of MTDH by shRNA reduced cell proliferation and enhanced cell apoptosis.
CONCLUSION
Lobaplatin was a safe and effective adjuvant chemotherapy for BCa. The effect of lobaplatin on inhibiting MCF-7 cell proliferation and inducing cell apoptosis might be, as least in part, mediated by suppressing the expression of oncogene MTDH.
Topics: Antineoplastic Agents; Apoptosis; Breast Neoplasms; Cell Adhesion Molecules; Cell Proliferation; Cyclobutanes; Down-Regulation; Female; Flow Cytometry; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; MCF-7 Cells; Membrane Proteins; Middle Aged; Organoplatinum Compounds; RNA-Binding Proteins; Real-Time Polymerase Chain Reaction; Tumor Cells, Cultured
PubMed: 30464390
DOI: 10.2147/DDDT.S163157