本文選題：ω-3多不飽和脂肪酸 + 維生素D�。� 參考：《江南大學(xué)》2017年碩士論文

【摘要】：乳腺癌是威脅女性健康的殺手之一。ω-3多不飽和脂肪酸在深海魚油中含量富足,很多流行病學(xué)調(diào)查報告顯示,長期攝入ω-3多不飽和脂肪酸能夠降低患有乳腺癌的風(fēng)險�，F(xiàn)階段認(rèn)為這是由于ω-3多不飽和脂肪酸可以抑制炎癥因子分泌和表皮生長因子的產(chǎn)生,從而可以促進(jìn)癌細(xì)胞的凋亡,并抑制癌細(xì)胞的生長和轉(zhuǎn)移。維生素D是人體不可或缺的脂溶性維生素之一,維生素D3是其活性形式,它不僅能夠調(diào)節(jié)鈣磷的代謝、改善骨骼發(fā)育,除此之外,維生素D可以調(diào)節(jié)細(xì)胞的周期蛋白,抑制癌細(xì)胞的增殖、促進(jìn)其細(xì)胞凋亡,具有一定的抗癌作用。但是ω-3多不飽和脂肪酸聯(lián)合維生素D對乳腺癌細(xì)胞的抑制作用是否能加強(qiáng),這一點還不清楚。本文主要觀察ω-3脂肪酸聯(lián)合維生素D3對三種類型乳腺癌細(xì)胞MCF-7(ER+,PR+)、SK-BR-3(HER2+)、MDA-MB-231(三陰性)的作用,并且對其相關(guān)機(jī)制進(jìn)行了探索。研究結(jié)果發(fā)現(xiàn),ω-3多不飽和脂肪酸和維生素D3都分別可以抑制三種乳腺癌細(xì)胞生長。ω-3脂肪酸聯(lián)合維生素D3后能夠加強(qiáng)對三種乳腺癌細(xì)胞的生長抑制作用,主要是通過抑制乳腺癌細(xì)胞增殖作用和促進(jìn)其細(xì)胞凋亡的方式。經(jīng)ω-3脂肪酸聯(lián)合維生素D3處理細(xì)胞后,MCF-7和SK-BR-3細(xì)胞中總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細(xì)胞中PARP和Bcl-2的蛋白水平?jīng)]有明顯變化。進(jìn)一步發(fā)現(xiàn)由Caspase的抑制劑預(yù)處理細(xì)胞后,聯(lián)合作用引起的MCF-7細(xì)胞凋亡減少,說明ω-3脂肪酸聯(lián)合維生素D3依賴Caspase信號來誘導(dǎo)MCF-7的細(xì)胞凋亡。另一方面,ω-3脂肪酸聯(lián)合維生素D3上調(diào)了MCF-7和SK-BR-3細(xì)胞p38和Erk1/2磷酸化水平,而在MDA-MB-231細(xì)胞中并無相同的發(fā)現(xiàn)。與此同時Raf-MAPK通路的激活和聯(lián)合引起的MCF-7細(xì)胞凋亡有關(guān),Raf和ASK-1激活在聯(lián)合誘導(dǎo)的p38和Erk1/2磷酸化水平上調(diào)中有著重要作用。下調(diào)shp2的表達(dá)觀察p38和Erk1/2磷酸化水平,發(fā)現(xiàn)兩者信號的反饋結(jié)果不盡相同,但也說明shp2部分參與了ω-3脂肪酸誘導(dǎo)的細(xì)胞凋亡的過程。以上結(jié)果也表明,ω-3脂肪酸聯(lián)合維生素D3誘導(dǎo)產(chǎn)生的細(xì)胞凋亡中,三種乳腺癌細(xì)胞所涉及的細(xì)胞通路不同。綜上所述,本文證明了ω-3多不飽和脂肪酸聯(lián)合維生素D3后都可以增加對三種乳腺癌細(xì)胞的生長抑制作用,但是聯(lián)合作用所引起三種乳腺癌細(xì)胞的信號通路不盡相同。
[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.
【學(xué)位授予單位】：江南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R737.9;TS201.4

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 羅年安;屈亞琦;董瑞;;乳腺癌的治療進(jìn)展[J];現(xiàn)代生物醫(yī)學(xué)進(jìn)展;2015年01期

2 包安裕;李艷;;維生素D抗癌作用機(jī)制研究進(jìn)展[J];國際檢驗醫(yī)學(xué)雜志;2013年23期

3 朱慧花;趙琳;;維生素D與免疫功能的研究[J];醫(yī)學(xué)綜述;2013年05期

4 黃哲宙;陳萬青;吳春曉;鄭榮壽;陳建國;程蘭萍;王寧;張思維;鄭瑩;;北京、上海、林州和啟東地區(qū)女性乳腺癌發(fā)病及死亡的時間趨勢[J];腫瘤;2012年08期

5 黃哲宙;陳萬青;吳春曉;鄭榮壽;陳建國;楊念念;王寧;張思維;鄭瑩;;中國女性乳腺癌的發(fā)病和死亡現(xiàn)況——全國32個腫瘤登記點2003—2007年資料分析報告[J];腫瘤;2012年06期

6 王覃;陳德才;;普通維生素D與骨質(zhì)疏松[J];中國實用內(nèi)科雜志;2011年07期

7 吳越;周曉玉;;與維生素D相關(guān)的臨床疾病研究進(jìn)展[J];中國實用兒科雜志;2010年01期

8 趙楊;趙林;郭科軍;陳波;溫放;;細(xì)胞外信號調(diào)節(jié)激酶在乳腺癌中的表達(dá)及意義[J];中國醫(yī)科大學(xué)學(xué)報;2007年03期

9 萬芳,鐘剛,何福仙,陳敏,關(guān)艷梅;ERK/MAPK信號通路激活與乳腺癌細(xì)胞浸潤性生長的關(guān)系[J];醫(yī)學(xué)研究生學(xué)報;2004年06期

10 楊守禮;維生素D研究的新趨勢——維生素D免疫學(xué)[J];中國骨質(zhì)疏松雜志;2004年01期

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