脾源性酪氨酸激酶抗肿瘤侵袭迁移的作用机制

The mechanism underlying the inhibitory effect of spleen tyrosine kinase on the invasion and migration of human breast cancer cells

目的:研究脾源性酪氨酸激酶(spleen tyrosine kinase,Syk)抗人乳腺癌肿瘤细胞的侵袭迁移能力,并对其作用机制进行初步探讨。方法:将全长SykcDNA经脂质体介导转染Syk表达阴性的高侵袭性人乳腺癌细胞MDA-MB-231,Transwell小室法检测转染前后肿瘤细胞侵袭迁移能力的变化,流式细胞术及酶联免疫吸附测定法检测与侵袭转移相关的血管内皮生长因子和基质金属蛋白酶-9的表达情况。结果:转染Syk全长基因的MDA-MB-231细胞与转染空载体及未转染的MDA-MB-231细胞相比,侵袭及迁移实验中的穿膜细胞数(总迁移细胞数/5个高倍视野)均明显减少(P<0.05);血管内皮生长因子及基质金属蛋白酶-9的表达量亦明显减少(P<0.05)。结论:转染SykcDNA可通过降低转染肿瘤细胞血管内皮生长因子及基质金属蛋白酶-9的表达,参与其抗肿瘤侵袭迁移作用。

Objective：To investigate the effect of spleen tyrosine kinase （Syk） on invasion and migration in human breast cancer cells and analyze its action mechanism. Methods. Full-length cDNA of Syk was transfected into Syk-negative human breast cancer cells MDA-MB-231 via liposome mediation. The invasion and migration ability of MDA-MB-231 cells was detected by Transwell ECM method. The expressions of invasion and migration-related molecule vasculars, endothelial growth factor （VEGF） and matrix metalloproteinaseses- 9 （ MMP-9）, were detected by flow cytometry （FCM） and enzyme-linked immunosorbant assy （ELISA） methods. Results：The number of membrane-passing cells every 5 high power fields was significantly decreased in Syk-transfected MDA-MB-231 cells compared with those transfected with blank vector or without transfection （ P 〈 0.05 ） . The expressions of VEGF and MMP-9 proteins were obviously reduced （P 〈 0.05）. Conclusion：Syk cDNA inhibited the invasion and migration of tumor cells by down-regulating the expressions of VEGF and MMP-9.