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.
Highlights
Ovarian cancer is one of the most common gynecologic malignancies (Suh et al, 2012)
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
Lobaplatin combined with docetaxel shows enhanced in-vitro cytotoxicity in the ovarian carcinoma cell lines
Summary
Ovarian cancer is one of the most common gynecologic malignancies (Suh et al, 2012). Because of rare specific symptoms and lack of feasible screening methods, more than two-thirds of patients with ovarian cancer are diagnosed at advanced-stage disease, which leads to poor prognosis. Taxanes and platinum-based chemotherapy after surgery has been established as the first line treatment by previous randomized controlled trials (Ozols et al, 2003; Suh et al, 2012). Cisplatin has nephrotoxicity, gastointestinal toxicity and neurotoxicity. Myelotoxicity, especially thrombocytopenia has been found to be the dose limiting toxicity of carboplatin. In ovarian cancer, carboplatin appears to have equivalent activity to cisplatin. Cisplatin and carboplatin are crossresistant (Alberts et al, 1989; Kim et al, 2011). New effective platinum-based chemotherapeutic agent with less toxicity and non-cross-resistance is needed for the treatment of ovarian cancer
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