Resveratrol (trans-3,4,5-trihydroxystilbene; RES) was adopted in this study as a novel phytoestrogen displaying antioxidant, antiinflammatory, and anticancer effects. In this study, we evaluated the inhibitory effect of RES on the cell growth induced by 17β-oestradiol (E2), a typical oestrogen, and bisphenol A (BPA), an endocrine-disrupting chemical (EDC) in BG-1 ovarian cancer cells expressing oestrogen receptors (ER) through down-regulating oestrogen receptor α (ERa) and insulin-like growth factor-1 receptor (IGF-1R). The EDC and oestrogen appear to promote the development of the oestrogen-dependent cancers. Thus, we need to develop therapeutic methods for EDC-dependent cancers. In in vitro experiments, we examined the cell viability and mRNA expression of ERa ± IGF-1R genes following the treatments with E2 or BPA in the presence or absence of RES or ICI 182 780, an ER antagonist, by MTT assay and RT-PCR, respectively. We also examined the protein level of ERa, phosphorylated insulin receptor substrate-1 (IRS-1), phosphorylated Akt1/2/3, p21, and cyclin D1 by Western blot analysis. Treatment with E2 or BPA remarkably increased the growth of BG-1 ovarian cancer cells, and their enhanced cell growth appeared to be mediated by ERa. In addition, the treatment of BG-1 ovarian cancer cells with E2 or BPA resulted in an increase in ERa and IGF-1R gene expressions. However, co-treatment of RES reversed E2- or BPA-induced ovarian cancer cell growth and mRNA expressions of ERa and IGF-1R. The protein levels of phosphorylated IRS-1 and Akt were upregulated by E2 or BPA, whereas these levels were downregulated by co-treatment of RES in the presence of E2 or BPA. Taken together, these results indicate that RES may effectively inhibit ovarian cancer cell growth via downregulating cross-talk between ERa and IGF-1R.
This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Ministry of Education, Science and Technology (MEST) of Korea government (no. 2011-0015385).
Insulin-like growth factor binding protein-2 stimulates proliferation and activates multiple cascades of the mitogen-activated protein kinase pathways in NIH-OVCAR3 human epithelial ovarian cancer cells
