阿托伐他汀对胰腺癌细胞PANC-1增殖、侵袭能力的影响及机制
Effects of atorvastatin on the proliferation and invasion of human pancreatic cancer cell PANC-1 and its mechanism study

摘要：目的 研究阿托伐他汀体外对胰腺癌细胞株PANC-1的影响及其机制。方法 不同浓度阿托伐他汀干预胰腺癌PANC-1细胞后，MTT法检测细胞的增殖、黏附作用，Transwell小室测定胰腺癌细胞的侵袭能力；RT-PCR方法测定MMP-2和VEGF的mRNA表达变化；Western blot方法检测ERK1/2的蛋白表达水平。结果 不同浓度阿托伐他汀干预胰腺癌PANC-1细胞后，细胞的增殖能力降低，并呈剂量时间依赖性。此外，阿托伐他汀可以抑制PANC-1细胞的黏附、侵袭能力，检测加药后PANC-1细胞内MMP-2、VEGF mRNA的相对表达量降低，与阴性对照组相比，差异有统计学意义(P=0.0013，P=0.007)，ERK1/2蛋白的相对表达量降低(P=0.0015)。结论 在体外细胞培养实验中，阿托伐他汀能显著抑制胰腺癌PANC-1细胞的增殖、黏附、侵袭能力，其机制可能是通过调控MAPK/ERK1/2通路减少MMP-2及VEGF的表达而实现。
ABSTRACT: Objective To investigate the effects of atorvastatin on the invasion and proliferation abilities of pancreatic cancer cell PANC-1. Methods PANC-1 cells were exposed to different concentrations of atorvastatin. We used MTT assay to detect the proliferation and adhesion capabilities of PANC-1 cells. Transwell chamber was used to detect the invasion ability of PANC-1 cells. The expressions of MMP-2 and VEGF mRNA were assayed by RT-PCR while the expression of ERK1/2 protein was assayed by Western blot. Results Different concentrations of atorvastatin could inhibit the proliferation, adhesion and invasion abilities of PANC-1 cells in a dose-dependent manner. Atorvastatin of 10 μmol/L inhibited the expressions of MMP-2 (P=0.0013), VEGF mRNA (P=0.007) and ERK1/2 protein (P=0.0015) significantly. Conclusion Atorvastatin significantly inhibits the proliferation, adhesion and invasion capabilities of PANC-1 cells in vitro. The mechanism may be related to inhibiting MAPK/ERK1/2 pathway and suppressing the expressions of MMP-2 and VEGF