Diindolylmethane (DIM) suppresses the growth of ovarian tumors alone and in combination with cisplatin by inhibiting signal transducer and activator of transcription 3 (STAT3) in nude mice. SKOV-3 tumor cells were implanted into athymic nude mice. Once each mouse had a palpable tumor, mice received 3 mg/day DIM by oral gavage every day or 5 mg/kg cisplatin intraperitoneally twice a week or both. (A) (i) Effect of DIM on tumor growth. *P < 0.05 when compared to control. (ii) Tumor weight of mice from different groups during the course of in vivo study. (B) Inhibition of STAT3 signaling in the tumors of mice administered with DIM alone or in combination with cisplatin. Tumors from control and treated mice were excised on day 48 after implantation, lysed and analyzed by western blotting for Tyr-705 STAT3, Ser-727 STAT3, total STAT3, Mcl-1, survivin, cleaved poly(ADP-ribose) polymerase (PARP) and cleaved caspase 3. Blots were stripped and reprobed with actin antibody to verify equal protein loading. Each lane represents a different tumor sample. (C) Densitometric quantitation of western blotting represented above. Legends on the bars indicate (a) statistically significant compared to control, (b) statistically significant compared to DIM, (c) statistically significant compared to cisplatin. (D) Levels of interleukin (IL)-6 in tumors from control mice and DIM treated mice. The differences between all the groups were compared by non-parametric analysis of variance with Bonferroni post hoc comparisons.