二甲双胍对肺腺癌A549细胞迁移及侵袭活性的影响  

Effects of antidiabetic drug metformin on the migration and invasion abilities of human lung adenocarcinoma A549 cell line in vitro

作　　者：武宁[1] 顾红军[2] 李强[1] 

机构地区：[1]第二军医大学附属长海医院呼吸内科,上海200433 [2]解放军第101医院苏州临床部内科,江苏苏州215007

出　　处：《中国癌症杂志》2009年第3期179-182,共4页China Oncology

摘　　要：背景与目的:二甲双胍是临床广泛应用的降糖药物。近年来的研究认为,该药物在调节机体糖类代谢的同时,还具有一定程度的抑制肿瘤细胞生长的作用。然而最近的研究结果提示,二甲双胍能促进肿瘤血管发生,可能促进肿瘤的早期转移。为了进一步明确二甲双胍与肿瘤转移的相关性,本研究对二甲双胍作用下人肺腺癌A549细胞的侧向迁移能力及体外侵袭能力的变化进行了检测,并初步探讨其可能的机制。方法:以不同浓度(0.5、2、8mmol/L)的二甲双胍处理A549细胞72h后,采用细胞划痕试验检测二甲双胍对A549细胞侧向迁移能力的影响;采用Boyden-Chamber分析法测定细胞的体外侵袭能力;Real-time PCR检测二甲双胍作用前后基质金属蛋白酶(MMP):MMP2和MMP9 mRNA的转录情况。结果:经较高浓度的二甲双胍(8mmol/L)干预72h后,人肺腺癌A549细胞的侧向迁移速度明显提高。二甲双胍8mmol/L组穿过基质胶的细胞数量明显增多(59.8±7.2),与对照组(37.4±4.6)相比差异有显著性(P<0.05)。而0.5mmol/L及2mmol/L组细胞的迁移及侵袭能力无明显改变。二甲双胍干预后,A549细胞内MMP2和MMP9的mRNA转录水平均明显增加,以8mmol/L组最为显著。结论:二甲双胍能增强人肺腺癌A549细胞的侧向迁移速度及体外侵袭能力,其机制可能与显著上调细胞内MMP2和MMP9的转录水平有关。Background and purpose： There is growing evidence that metformin, a commonly used drug in the treatment of type Ⅱ diabetes, may impede the growth of human tumors. However in a recent study it was found that metformin treatment might result in promotion of the angiogenic phenotype and increase tumorigenic progression. In this study we investigated the effects of metformin on the migration and invasion abilities of human lung adenocarcinoma cell line A549 in vitro and explored the possible underlying mechanisms. Methods： A549 cells were treated with 0.5, 2 and 8 mmol/L metformin for 72 hrs. The laterad-migration and invasion abilities of the cells in vitro were measured by scratch assay and Boyden-Chamber assay, respectively. Expressions of MMP2 and MMP9 mRNA of the cells before and after metformin treatment were measured by Real-time PCR. Results： The migration rate of A549 cells was increased after treated by metformin at the concentration of 8 mmol/L. The invasion ability was also significantly increased by 8 mmol/L metformin treatment from 37.4±4.6 to 59.8±7.2（P〈0.05）. No significant differences in the migration and invasion abilities were observed between the Group 0,5 mmol/L or 2 mmol/L and the Control. The expressions of MMP2 and MMP9 mRNA were both up-regulated after metformin treatment while in Group 8 mmol/L the changes of the genes were most significant. Conclusion： Metformin can increase the migration and invasion abilities of A549 cells in vitro, which may be attributed to the up-regulation of MMP2 and MMP9.

关 键 词：肺腺癌 二甲双胍 迁移 侵袭能力 MMP2 MMP9 

分 类 号：R734.2[医药卫生—肿瘤] R587.1[医药卫生—临床医学]