title: Combination of Tetrandrine with cisplatin enhances cytotoxicity through growth suppression and apoptosis in ovarian cancer in vitro and in vivo.
abstract: Cisplatin, as a first-line drug in the chemotherapy of ovarian cancer, poses significant problems in its toxicity to normal tissue and drug resistance. Here, we report that Tetrandrine, with potent anti-cancer effect, significantly enhances the cytotoxicity of cisplatin in ovarian cancer. The in vitro assay indicates that Tetrandrine can markedly increase growth suppression and apoptosis induced by cisplatin and cause redistribution of the cell cycle. Further assay indicates that modulation of Wnt/cadherin signaling pathway contributes to the chemosensitizing effect of Tetrandrine on the cytotoxicity of cisplatin in ovarian cancer. In vivo, the combination of Tetrandrine and cisplatin exhibits the strongest anti-cancer effect compared with each drug alone, with no obvious additional toxicity. These results provide rational evidence supporting the application of Tetrandrine as an adjunct to cisplatin in improvement of chemotherapy in ovarian cancer.
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Yuxing
authors.initials: Y
authors.lastname: Zhang
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.forename: Haiwei
authors.initials: H
authors.lastname: Wang
authors.forename: Kankan
authors.initials: K
authors.lastname: Wang
authors.forename: Yanzhi
authors.initials: Y
authors.lastname: Du
authors.forename: Ji
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D044182:Benzylisoquinolines / Q000008:administration & dosage; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin / Q000008:administration & dosage; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D044182:Benzylisoquinolines; C009438:tetrandrine; D002945:Cisplatin