Omega-3多不饱和脂肪酸联合维生素D对乳腺癌细胞的作用

发布时间：2018-05-14 03:07

本文选题：ω-3多不饱和脂肪酸 + 维生素D　；参考：《江南大学》2017年硕士论文

【摘要】：乳腺癌是威胁女性健康的杀手之一。ω-3多不饱和脂肪酸在深海鱼油中含量富足,很多流行病学调查报告显示,长期摄入ω-3多不饱和脂肪酸能够降低患有乳腺癌的风险。现阶段认为这是由于ω-3多不饱和脂肪酸可以抑制炎症因子分泌和表皮生长因子的产生,从而可以促进癌细胞的凋亡,并抑制癌细胞的生长和转移。维生素D是人体不可或缺的脂溶性维生素之一,维生素D3是其活性形式,它不仅能够调节钙磷的代谢、改善骨骼发育,除此之外,维生素D可以调节细胞的周期蛋白,抑制癌细胞的增殖、促进其细胞凋亡,具有一定的抗癌作用。但是ω-3多不饱和脂肪酸联合维生素D对乳腺癌细胞的抑制作用是否能加强,这一点还不清楚。本文主要观察ω-3脂肪酸联合维生素D3对三种类型乳腺癌细胞MCF-7(ER+,PR+)、SK-BR-3(HER2+)、MDA-MB-231(三阴性)的作用,并且对其相关机制进行了探索。研究结果发现,ω-3多不饱和脂肪酸和维生素D3都分别可以抑制三种乳腺癌细胞生长。ω-3脂肪酸联合维生素D3后能够加强对三种乳腺癌细胞的生长抑制作用,主要是通过抑制乳腺癌细胞增殖作用和促进其细胞凋亡的方式。经ω-3脂肪酸联合维生素D3处理细胞后,MCF-7和SK-BR-3细胞中总PARP和Bcl-2的蛋白水平下降,MCF-7中剪切型PARP的蛋白水平上升,但是MDA-MB-231细胞中PARP和Bcl-2的蛋白水平没有明显变化。进一步发现由Caspase的抑制剂预处理细胞后,联合作用引起的MCF-7细胞凋亡减少,说明ω-3脂肪酸联合维生素D3依赖Caspase信号来诱导MCF-7的细胞凋亡。另一方面,ω-3脂肪酸联合维生素D3上调了MCF-7和SK-BR-3细胞p38和Erk1/2磷酸化水平,而在MDA-MB-231细胞中并无相同的发现。与此同时Raf-MAPK通路的激活和联合引起的MCF-7细胞凋亡有关,Raf和ASK-1激活在联合诱导的p38和Erk1/2磷酸化水平上调中有着重要作用。下调shp2的表达观察p38和Erk1/2磷酸化水平,发现两者信号的反馈结果不尽相同,但也说明shp2部分参与了ω-3脂肪酸诱导的细胞凋亡的过程。以上结果也表明,ω-3脂肪酸联合维生素D3诱导产生的细胞凋亡中,三种乳腺癌细胞所涉及的细胞通路不同。综上所述,本文证明了ω-3多不饱和脂肪酸联合维生素D3后都可以增加对三种乳腺癌细胞的生长抑制作用,但是联合作用所引起三种乳腺癌细胞的信号通路不尽相同。
[Abstract]:Breast cancer is one of the killers of women's health. 蠅 -3 polyunsaturated fatty acids are abundant in deep-sea fish oil, and many epidemiological reports show that long-term intake of 蠅 -3 polyunsaturated fatty acids can reduce the risk of breast cancer. It is believed that 蠅 -3 polyunsaturated fatty acids can inhibit the secretion of inflammatory factors and the production of epidermal growth factors, which can promote the apoptosis of cancer cells and inhibit the growth and metastasis of cancer cells. Vitamin D is one of the indispensable liposoluble vitamins in human body, vitamin D3 is its active form, it can not only regulate the metabolism of calcium and phosphorus, but also improve the bone development. In addition, vitamin D can regulate the cell cycle protein. Inhibit the proliferation of cancer cells, promote their apoptosis, has a certain anti-cancer effect. But it is not clear whether 蠅-3 polyunsaturated fatty acids combined with vitamin D can enhance the inhibition of breast cancer cells. The effects of omega-3 fatty acids combined with vitamin D3 on MDA-MB-231MDA-MB-231in three types of breast cancer cells were studied and the related mechanisms were explored. The results showed that 蠅 -3 polyunsaturated fatty acids and vitamin D 3 could inhibit the growth of three kinds of breast cancer cells, and 蠅 -3 fatty acids combined with vitamin D 3 could enhance the growth inhibition of three kinds of breast cancer cells. Mainly by inhibiting the proliferation of breast cancer cells and promoting their apoptosis. After treated with 蠅 -3 fatty acid and vitamin D3, the protein levels of total PARP and Bcl-2 in MCF-7 and SK-BR-3 cells decreased, while the protein level of shear type PARP in MCF-7 increased, but the protein levels of PARP and Bcl-2 in MDA-MB-231 cells did not change significantly. It was further found that the apoptosis of MCF-7 cells induced by co-treatment with Caspase inhibitor was decreased, which indicated that 蠅 -3 fatty acids combined with vitamin D3 depended on Caspase signal to induce the apoptosis of MCF-7 cells. On the other hand, omega-3 fatty acids combined with vitamin D3 up-regulated the phosphorylation levels of p38 and Erk1/2 in MCF-7 and SK-BR-3 cells, but there was no similar finding in MDA-MB-231 cells. At the same time, activation of Raf-MAPK pathway and co-induced apoptosis of MCF-7 cells may play an important role in co-induced up-regulation of p38 and Erk1/2 phosphorylation. Down-regulation of shp2 expression observed the phosphorylation level of p38 and Erk1/2 and found that the feedback results of the two signals were different, but it also indicated that shp2 partly participated in the apoptosis induced by omega-3 fatty acids. These results also indicated that the apoptosis induced by omega-3 fatty acids combined with vitamin D _ 3 may involve different cellular pathways in breast cancer cells. To sum up, it is proved that 蠅 -3 polyunsaturated fatty acids combined with vitamin D 3 can increase the growth inhibition of three kinds of breast cancer cells, but the signal pathways of the three kinds of breast cancer cells caused by the combination action are different.
【学位授予单位】：江南大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.9;TS201.4

【参考文献】