The antitumor effect of lobaplatin against Ishikawa endometrial cancer cells in vitro and in vivo.

Abstract

The new effective chemotherapeutic drugs are required urgently for advanced and recurrent endometrial carcinoma (EC), which is one of the most common gynaecological tumors among women worldwide. Preclinical studies have shown that lobaplatin, one of the third-generation platinum compounds, has possessed powerful anti-cancer efficacy on a series of tumors. The purpose of this study is to investigate its effect and molecular mechanism on the growth of endometrial cancer cell line Ishikawa in vitro and in vivo. The results of cell counting kit-8 (CCK-8) shown that lobaplatin concentration-dependent inhibited cell proliferations in human endometrial carcinoma ishikawa cells. Flow cytometry (FCM) assay demonstrated that lobaplatin affected the survival of endometrial carcinoma cell by arresting cell cycle at S phase and G2/M phase and inducing apoptosis in dose-dependent manner. Moreover, Western blot analysis also showed that the apoptosis-inducing effects of lobaplatin was associated with the reduction of Bcl-2 expression while upregulation of cleaved-caspase-3, cleaved-caspase-8, cleaved-caspase-9 and Bax. Meanwhile, lobaplatin significantly suppressed tumor growth of human Ishikawa xenograft models and terminal deoxynucleotidyl trans-ferase dUTP nick end labeling confirmed the significant occurrence of lobaplatin-treated tumor tissues of apoptosis. Therefore, lobaplatin could be an effective chemotherapeutic agent for human endometrial carcinoma and warrants further clinical investigation.

• Authors: Jingchao He, Haijun Zhang
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 114 Pg. 108762 (Jun 2019) ISSN: 1950-6007 [Electronic] France
• PMID: 30925454 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Antineoplastic Agents
• Cyclobutanes
• Organoplatinum Compounds
• lobaplatin

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cyclobutanes (pharmacology)
• Endometrial Neoplasms (drug therapy, metabolism)
• Endometrium (drug effects, metabolism)
• Female
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Recurrence, Local (drug therapy, metabolism)
• Organoplatinum Compounds (pharmacology)
• Signal Transduction
• Up-Regulation (drug effects)
• Xenograft Model Antitumor Assays (methods)