血管紧张素诱导MMP-2和MMP-9在人结肠癌细胞中的表达

Expression of MMP-2 and MMP-9 induced by angiotensin in human colon cancer cell lines

目的研究血管紧张素Ⅱ(AngⅡ)对人结肠癌细胞基质金属蛋白酶2(MMP-2)和基质金属蛋白酶-9(MMP-9)表达的影响。方法筛选出AT1受体(AT1R)高表达的结肠癌细胞株,采用不同浓度的AngⅡ进行处理,收集不同时点的细胞,提取细胞总RNA和总蛋白。采用实时PCR和Western blotting,分别检测AngⅡ处理前后结肠癌细胞MMP-2、MMP-9 mRNA以及相应编码蛋白的表达变化,研究AngⅡ对MMPs表达的诱导作用。结果AT1R在多数结肠癌细胞株中有表达,以LoVo细胞最为明显。AngⅡ能够刺激LoVo细胞MMP-2、MMP-9 mRNA和蛋白的表达,并呈剂量和时间依赖效应。Lovo细胞MMP-2、MMP-9蛋白表达水平的上调能被AT1R拮抗剂阻断。结论AngⅡ可以通过AT1R诱导人结肠癌细胞MMP-2和MMP-9的表达,在肿瘤的转移机制中可能具有一定的作用。

Objective To investigate the effects of angiotensin（Ang） Ⅱ on the expression of matrix metalloproteinase （MMP）-2 and MMP-9 in human colon cancer cell lines. Methods Colon cancer cell lines with high level of Ang Ⅱ type1 receptor （ATlR） expression were screened and treated with different concentrations of Ang Ⅱ . Cells were collected at different time points and total RNA and total protein were extracted. The expressions of MMP-2 and MMP-9 mRNA and protein were detected by real-time PCR and Western blotting before and after the treatment, and the induction of MMPs by Ang Ⅱ was analysed. Results ATlR was observed in most of the colon cell lines, with Lovo being the most highly-expressed one. Ang Ⅱ induced MMP-2 and MMP-9 mRNA and protein expressions in a dose- and time-dependent manner in Lovo cells, and this effect could be suppressed by ATlR antagonist. Conclusion The expression of MMP-2 and MMP-9 can be induced by Ang Ⅱ in human colon cancer cell lines through ATlR, which may play a definite role in the tumor metastasis.