title: Preclinical activity of lobaplatin as a single agent and in combination with taxanes for ovarian carcinoma cells.
abstract: Lobaplatin, one of the third-generation platinum compounds, has shown encouraging anticancer activity in a variety of tumor types. However, the efficacy of lobaplatin in ovarian cancer has not been systemically evaluated. In this study, lobaplatin as a single agent and in combination with taxanes was investigated in-vitro and in an in vitro model of ovarian carcinoma. Using the sulforhodamine B (SRB) assay, the cytotoxic effects of lobaplatin alone and in combination with taxanes were compared with cisplatin and carboplatin in seven ovarian cancer cell lines. In addition, in-vitro antitumor activities were evaluated with cisplatin-sensitive and cisplatin-resistant human ovarian cancer xenografts in nude mice. The cytotoxicity of lobaplatin was similar to or higher than that of cisplatin and carboplatin, with IC50 values from 0.9 to 13.8 μmol/L in a variety of ovarian cancer cells. The combination of lobaplatin with docetaxel yielded enhanced cytotoxic activity in vitro. In addition, in platinum-sensitive ovarian cancer xenografts, lobaplatin alone showed similar antitumor activity to cisplatin and carboplatin. Furthermore, lobaplatin alone or in combination with docetaxel exhibited significant activity in platinum-resistant ovarian cancer xenografts. These results indicate that the use of lobaplatin alone or in combination with docetaxel might be a rational and novel therapeutic strategy for ovarian cancer. Further clinical development of lobaplatin is clearly warranted.
authors.affiliation: The Clinical Department, Guizhou Yibai Pharmaceutical Co.Ltd, Guiyang, China E-mail : lglou@mail.shcnc.ac.cn; suidonghu@sohu.com.
authors.forename: Xu
authors.initials: X
authors.lastname: Sun
authors.forename: Li-Guang
authors.initials: LG
authors.lastname: Lou
authors.forename: Dong-Hu
authors.initials: DH
authors.lastname: Sui
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Wu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D003503:Cyclobutanes / Q000494:pharmacology*; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D003503:Cyclobutanes; D009944:Organoplatinum Compounds; D043823:Taxoids; D000077143:Docetaxel; C066228:lobaplatin; D002945:Cisplatin