以高糖及油酸誘導血管平滑肌細胞及乳癌細胞增生移行的相關機轉

Oleic Acid and Glucose Induced Vascular Smooth Muscle Cell and Breast Cancer Cell Proliferation and Migration and its Mechanisms

楊宜瑱(Yi-Sun Yang)

指導教授 ： 黃建寧

中山醫學大學/醫學院/醫學研究所/博士(2014年)

https://doi.org/10.6834/CSMU.2014.00179

摘要

本研究目的是探討高糖及油酸對人血管平滑肌细胞(VSMCs)和人乳腺癌細胞細胞(MDA-MB-231 cell) 對結締組織生長因子和脂肪酸合成酶的表現及其相關機轉。VSMCs和MDA-MB-231 cell分别與不同濃度的葡萄糖(25~30mmol/L) 及油酸 (200 uM)培養，用Western blot方法檢測葡萄糖及油酸對人血管平滑肌细胞和人乳腺癌細胞細胞的結締組織生長因子和脂肪酸合成酶的影響。研究結果顯示油酸會刺激血管平滑肌細胞的增生和移行。經油酸所誘導的血管平滑肌细胞增生是經由結締組織生長因子/脂肪酸合成酶所調控；而移行則是由結締組織生長因子所調控，其作用機制可能油酸增加的focal adhesion kinase信號通路有關。另一方面，在乳癌細胞的研究，我們的研究結果發現，葡萄糖誘導的增生是由脂肪酸合成酶所調控，而油酸誘導的增生則是由結締組織生長因子所調控。油酸和葡萄糖同時能誘導vimentin，影響細胞遷移，而可被metformin抑制。綜合以上結果，這研究證明高糖及油酸對人血管平滑肌细胞(VSMCs)和人乳腺癌細胞細胞(MDA-MB-231 cell) 的增生及移行皆透過結締組織生長因子和脂肪酸合成酶來調控。Metformin可能扮演抑制乳癌細胞侵襲的角色。

關鍵字

油酸 ； 高糖 ； 結締組織生長因子 ； 脂肪酸合成酶血管平滑肌細胞乳癌細胞

並列摘要

To investigate the role of glucose and oleic acid in the expression of connective tissue growth factor (CTGF) and fatty acid synthase (FASN) in human vascular smooth muscle cells (VSMCs) and breast cancer cells (MDA-MB-231 cell) and its possible mechanisms. VSMCs and MDA-MB-231 cell were incubated in the presence of glucose, oleic acid and both at the concentrations ranging from 25 to 30 mM and oleic acid of 200 uM, and Western blotting was used to measure the protein expressions of CTGF and FASN. Oleic acid could induce both migration and proliferation of VSMCs and MDA-MN-231 cells. Oleic acid induced VSMCs proliferation is mediated by CTGF and FASN, whereas migration is mediated by CTGF, by activating focal adhesion kinase. Glucose induced MDA-MB-231 cells proliferation is mediated by FASN, whereas oleic acid induced proliferation is mediated by CTGF. Both glucose and oleic acid increased the vimentin expression, which could be inhibited by metformin. Glucose and oleic acid could induce both migration and proliferation of VSMCs and MDA-MB-231 cells, mediated by CTGF and FASN. Metformin could play a role of inhibit breast cells invasion.

並列關鍵字

Glucose ； oleic acid ； vascular smooth muscle cell ； breast cancer cell connective tissue growth factor ； fatty acid synthase

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