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 activityin a variety of tumor types. However, the efficacy of lobaplatin in ovarian cancer has not been systemicallyevaluated. In this study, lobaplatin as a single agent and in combination with taxanes was investigated in - vitroand in an in vitro model of ovarian carcinoma. Using the sulforhodamine B (SRB) assay, the cytotoxic effects oflobaplatin alone and in combination with taxanes were compared with cisplatin and carboplatin in seven ovariancancer 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 higherthan that of cisplatin and carboplatin, with IC50 values from 0.9 to 13.8 μmol/L in a variety of ovarian cancercells. The combination of lobaplatin with docetaxel yielded enhanced cytotoxic activity in vitro. In addition, inplatinum - sensitive ovarian cancer xenografts, lobaplatin alone showed similar antitumor activity to cisplatinand carboplatin. Furthermore, lobaplatin alone or in combination with docetaxel exhibited significant activityin platinum - resistant ovarian cancer xenografts. These results indicate that the use of lobaplatin alone or incombination with docetaxel might be a rational and novel therapeutic strategy for ovarian cancer. Furtherclinical development of lobaplatin is clearly warranted.