Cisplatin is considered as a well established platinum drug used to treat various cancers, including ovarian cancer. However, Patients treated with cisplatin often produce resistance to the treatment, and higher doses cisplatin will exert side effects such as nephrotoxicity and ototoxicity in patients. STAT3 has been found to overexpress in various tumors, including ovarian tumors, and the overexpression is reported to be positively associated with cisplatin resistance, thus it represents an attractive target for intervention.
3,3’-Diindolylmethane (DIM) from cruciferous vegetables shows the chemopreventive and therapeutic properties with non-toxic to normal cells, and exhibits antiproliferative properties in ovarian cancer cells. In the recent paper, Kandala et al. report the mechanism of DIM action in ovarian cancer cells. The results show that DIM induces apoptosis in ovarian cancer cells, and inhibits STAT3 pathway in ovarian cancer cells, as well as the expression of Mcl-1 and survivin. In addition, DIM inhibits nuclear translocation of STAT3, DNA binding activity and transcriptional activity of STAT3. Besides, inhibition of STAT3 abrogates DIM-induced apoptosis, while IL-6-induced STAT3 activation significantly blocks DIM-induced apoptosis. Further study demonstrates that combination treatment of DIM and cisplatin abolishes the STAT3 phosphorylation and reduces the expression of STAT3, which lead to the inhibiton of ovarian tumor growth.
In summary, DIM can target STAT3 to suppress the growth of ovarian tumor cells, and potentiate the effect of cisplatin on the treatment of the ovarian tumor.