Objective      To evaluate the effects of 3

3′-diindolylmethane (DIM) on the proliferation and apoptosis

of human ovarian cancer cell lines SKOV3 and A2780

study the expression of signal transducer and activator of transcription 3 (STAT3)

p-STAT3 and the proteins related to apoptosis

  and determine the role of STAT3 pathway in the antitumor activity of DIM.       Methods      MTT assay was used to examine the effects of DIM at different concentrations (50

100

200

and 400 μmol/L) and for different time periods (24

48

72  and 96 h) on the proliferation of SKOV3 and A2780 cells. Inversion phase contrast microscopy and Hoechst 33342 staining was used to observe the apoptosis changes of cell morphology. Flow cytometry was used to analyze the apoptotic rate and cell cycle. Western blotting was used to detect the protein levels of STAT3

p-STAT3

caspase-3

mcl-1

and survivin in SKOV3 cells treated with DIM of different concentrations.       Results      Compared with the control group

DIM could significantly inhibit the proliferation of SKOV3 and A2780 cells in time- and dose-dependent manners (

P

0.05 or

P

0.01). The apoptotic rate in SKOV3 cells was (5.16±2.07)%

(16.41±3.58)%

and (31.58±12.35)% 48h after treatment by 0

100 and 150 μmol/L DIM

respectively. Cell cycle analysis indicated that the percentage of A2780 cells in G

1

/G

2

phase was increased and that in S phase was decreased after 75  μmol/L DIM treatment for 24 h. DIM also up-regulated the expression of caspase 3 protein (

P

0.05) and down-regulated the expression of mcl-1

survivin and p-STAT3 protein (

P

0.05). However

there was no change in the level of total STAT3 protein expression after the DIM treatment.       Conclusion      DIM can effectively inhibit the proliferation and induce the apoptosis in SKOV3 and A2780 cells. The DIM-induced apoptosis may be related to the inhibition of STAT3 activity and then the expression down-regulation of  mcl-1 and survivin as well as up-regulation of caspase 3. DIM might be used as a preventive and therapeutic agent against human ovarian cancer.