Cisplatin resistance remains one of the major obstacles when treating
epithelial ovarian cancer. Because
oxaliplatin and nedaplatin are effective against
cisplatin-resistant
ovarian cancer in clinical trials and
signal transducer and activator of transcription 3 (STAT3) is associated with
cisplatin resistance, we investigated whether overcoming
cisplatin resistance by
oxaliplatin and nedaplatin was associated with the STAT3 pathway in
ovarian cancer. Alamar blue, clonogenic, and
wound healing assays, and
Western blot analysis were used to compare the effects of
platinum drugs in SKOV-3
cells. At an equitoxic
dose,
oxaliplatin and nedaplatin exhibited
similar inhibitory effects on colony-forming
ability and greater inhibition on
cell motility than
cisplatin in
ovarian cancer. Early in the
time course of
drug administration,
cisplatin increased the expression of pSTAT3 (Tyr705), STAT3α,
VEGF,
survivin, and Bcl-XL, while
oxaliplatin and nedaplatin exhibited the opposite effects, and upregulated pSTAT3 (Ser727) and STAT3β. The STAT3 pathway responded early to
platinum drugs associated with
cisplatin resistance in
epithelial ovarian cancer and provided a rationale for new
therapeutic strategies to reverse
cisplatin resistance.