3,3’-Diindolylmethane inhibits ovarian cancer cell viability and enhances chemotherapy sensitivity via STAT3 Pathway

Purpose: Ovarian cancer is the leading cause of gynecologic cancer deaths among women. 3, 3’-diindolylmethane(DIM), a small molecule compound, is a proposed cancer preventive agent without causing toxicity to normal cells. Signal transducer and activator of transcription-3 (STAT3)was constitutively activated in ovarian cancer .In the present study, we aimed at investigate the potential effects of DIM on ovarian cancer cells and observe the effects of the combination of STAT3 gene silencing and DIM on cell viability, cell-cycle regulation, and sensitivity to chemotherapy. Methods: Ovarian cancer SKOV3 and A2780 cell lines were treated with various concentrations of DIM for different periods of time for assessment of cell viability, and sensitivity to chemotherapy as well as gene expression before and after knockdown of STAT3 expression using STAT3 shRNA. Results: The study find DIM treatment potently suppressed abilities of ovarian cancer cell viability, also induced cisplatin sensitivity. At the gene level, DIM inhibited phosphorylation of STAT3 proteins and expression of its downstream proteins. Moreover, knockdown of STAT3 expression significantly enhanced DIM antitumor activity and cisplatin sensitivity. In addition, their combination suppressed expression of survivin, Bcl-2, Mcl-1, but upregulated expression of Caspase3. Conclusions: Our findings suggest DIM antitumor activity was to inhibit the STAT3 signaling pathways. The combination of STAT3 knockdown with DIM treatment could be further evaluated as a therapeutic strategy for treatment of advanced ovarian cancer.