| Breast cancer is one of the killers which threaten women’s health.ω-3 polyunsaturated fatty acids are rich in deep-sea fish oil,and many epidemiological studies have shown that long-term intake of ω-3 polyunsaturated fatty acids could reduce the risk of breast cancer.It is now accepted that ω-3 polyunsaturated fatty acids can inhibit the secretion of inflammatory factors and epidermal growth factor production,which can promote cancer cell apoptosis,and inhibit cancer cell growth and metastasis.Vitamin D is one of the indispensable fat-soluble vitamins,and vitamin D3 is an active form of vitamin D,which can not only regulate the metabolism of calcium and phosphorus but also promote bone development.In addition,vitamin D can regulate the cell cycle protein to inhibit the proliferation of cancer cells,and promote cancer cells apoptosis,which makes vitamin D a certain anti-cancer effect.However,it is unclear whether the combination of ω-3 polyunsaturated fatty acids and vitamin D has a stronger effect on suppression of breast cancer cells.This study observed the effect of ω-3 fatty acids combined with vitamin D3 on three subtypes of breast cancer cells: MCF-7(ER+,PR+),SK-BR-3(HER2+),MDA-MB-231(triple-negative),and their related mechanisms were explored too.The results showed that ω-3 polyunsaturated fatty acids and vitamin D3 could inhibit the growth of three breast cancer cell lines respectively.ω-3 fatty acids combined with vitamin D3 enhanced the growth inhibition of three breast cancer cell lines,mainly by suppressing breast cancer cell proliferation and promoting cell apoptosis.The levels of total PARP and Bcl-2 in MCF-7 and SK-BR-3 cell lines were decreased after the combination of ω-3 fatty acids and vitamin D3,and the level of cleaved PARP in MCF-7 was increased,but not in MDA-MB-231.It was found that after treatment with an inhibitor of Caspases,survival cells were increased,indicating that cell apoptosis induced by the combination in MCF-7 was dependent on Caspase signals.On the other hand,ω-3 fatty acids combined with vitamin D3 increased the phosphorylation of p38 and Erk1/2 levels in MCF-7 and SK-BR-3 cell lines,but had no similar discovery in MDA-MB-231 cells.At the same time,it was found that the activation of Raf-MAPK pathway was related to the induction of cell apoptosis in MCF-7.Raf and ASK-1 had an important role in the up-regulation of p38 and Erk1/2 phosphorylations.After down-regulation of shp2 expression,p38 and Erk1/2 phosphorylations were found to be different in different cell lines,but it also indicated that shp2 played an important role in ω-3 fatty acids-induced apoptosis.The above results also showed that ω-3 fatty acids combined with vitamin D3 resulted in cell apoptosis causing participation of different pathways in the three breast cancer cell lines.In summary,this paper demonstrated that ω-3 polyunsaturated fatty acids combined with vitamin D3 enhanced the inhibition of cell growth in three breast cancer cell lines,but it was caused by different pathways in different cells. |