Simultaneous suppression of Src and signal transducer and activator of transcription 3 inhibits the growth of epithelial ovarian cancer cells

Objective: The reciprocal regulation of c-Src and STAT3 activation seems to be associated with the poor response to c-Src inhibitors of ovarian cancer. This study aims to investigate inhibition of cell proliferation and enhancement of the cytotoxic effect of chemotherapeutic agents via simultaneous suppression of c-Src and STAT3 in ovarian cancer cell lines. Study design: Specific siRNAs targeting c-Src and STAT3 were produced and transfected into an SKOV3 ovarian cancer cell line. We confirmed the downregulation of c-Src and STAT3 mRNAs by reverse transcriptase polymerase chain reaction. MTT assay was used to assess cytotoxicity following cisplatin administration. Protein expression level was evaluated by Western blot. Results: Cell growth was significantly inhibited by c-Src or STAT3 siRNA. Cytotoxicity was not increased in cisplatin-treated SKOV3 by c-Src siRNA only or STAT3 siRNA only, but cell viability was decreased significantly in cisplatin-treated cells after simultaneous transfection with c-Src and STAT3 siRNAs. Specifically, the viability was significantly decreased from 30% to 55% within the IC ₅₀ concentration following simultaneous transfection with c-Src and STAT3 siRNAs, particularly after 72 h. Src and survivin protein expression level was significantly decreased at 72 h after transfection of c-Src and STAT3 siRNAs. Conclusions: This study has demonstrated the principle that the simultaneous suppression of c-Src and STAT3 inhibits the growth of epithelial ovarian cancer cells and seems to enhance the cytotoxicity of chemotherapeutic agents in ovarian cancer.