The Effects Of Omega-3 Fatty Acids And Vitamin D On Breast Cancer Cells Insulin Signaling Pathway

Insulin is closely related with breast tumorigenesis, it could not only regulate the energy metabolism but also promote cell growth. High circulating insulin induces cell excessive proliferation and promotes the secretion of estrogen to enhance breast tumorigenesis. Epidemiology results showed that breast cancer risk was decreased by consumption of fish oils which contain ω-3 polyunsaturated fatty acids（PUFAs）. The ω-3PUFAs have been recognized to induce cell apoptosis and suppress cell proliferation through the inhibition of secretion of inflammatory cytokines and epidermal growth factor. However, whether ω-3PUFAs decrease the risk of breast cancer by inhibiting insulin-induced breast cancer cells growth is unclear. To address this question, this paper found that MCF-7 breast cancer cells growth was dramatically increased by insulin treatment and ω-3PUFAs inhibited cells growth and induced cells apoptosis. ω-3PUFAs combined with insulin attenuated insulin-stimulated MCF-7 cells growth. Furthermore, insulin promoted Akt and Erk1/2 activation of MCF-7 cells but ω-3PUFAs attenuated insulin-stimulated Akt and Erk1/2 activation. To investigate the molecular mechanism of ω-3PUFAs disrupted insulin signaling, shp2, Erk1/2 and Akt upstream, was knockdown by shp2 siRNA. The inhibition of ω-3PUFAs to insulin-stimulated cells growth and the regulation of ω-3PUFAs to Erk1/2 activation were uninfluenced by knockdown of shp2, suggesting that shp2 was not involved in the inhibition of ω-3PUFAs to insulin-activated Akt and Erk1/2 signals. Meanwhile, cell proliferation and apoptosis regulated by ω-3PUFAs were unchanged by knockdown of shp2 or Erk1/2 inhibitor U0126 treatment, suggesting that shp2/Erk1/2 signaling was not involved in the fatty acids pathway, but shp2 inhibited ω-3PUFAs-stimulated Akt activation.Vitamin D₃, one of fat soluble vitamins, not only regulates calcium and phosphorus metabolism but also suppresses cell growth by inhibiting cancer cells entry into DNA synthesis phase. Importantly, Vitamin D₃ could inhibit insulin induced MCF-7 cells growth. This paper showed here that Vitamin D₃ enhanced the repression of ω-3PUFAs on MCF-7 cells growth and insulin signaling.In conclusion, ω-3PUFAs could attenuate insulin-stimulated MCF-7 cells growth and disrupted MCF-7 cells insulin signaling, Vitamin D₃ enhanced these effects of ω-3PUFAs.