二甲双胍联合照射抑制人肺癌细胞的侵袭和转移的研究  

Inhibition of lung cancer cells migration and invasion by metformin combined with irradiation

作　　者：王雯珺[1] 列璞怡[1] 郭敏章 何建行[1] 

机构地区：[1]呼吸疾病国家重点实验室/广州医科大学附属第一医院,广东广州510120

出　　处：《河南医学研究》2016年第5期777-780,共4页Henan Medical Research

基　　金：国家自然科学基金(81301939);博士后基金(2015M570697)

摘　　要：目的探讨二甲双胍联合照射对人肺癌细胞的侵袭和转移能力的影响,为研发肺癌有效的靶向治疗方案提供新思路。方法应用MTT法检测二甲双胍联合照射对肺癌肿瘤细胞的抑制作用,划痕和侵袭实验观察肿瘤细胞迁移和侵袭能力的改变,Western blot检测其侵袭转移相关因子MMP-2、MMP-9、VEGF的表达情况。结果 MTT显示,不同浓度的二甲双胍对肺癌细胞A549具有显著的增殖抑制作用。二甲双胍组、照射组和联合处理组12 h和24 h的迁移距离均低于对照组。联合处理组作用于A549细胞的侵袭抑制作用也明显高于单用二甲双胍组和照射组。联合处理组可下调MMP-2、MMP-9和VEGF的表达。结论二甲双胍降低了肺癌肿瘤细胞的生长,下调了MMP-2、MMP-9、VEGF的表达,并有效抑制肺癌细胞的侵袭能力,提示二甲双胍在肺癌转移过程中起重要作用,可以作为肺癌的潜在治疗方案。Objective To investigate the effect of metformin combined with irradiate on migration and invasion capacity in lung cancer so as to shed new light on the development of target therapy for lung cancer. Methods Inhibitory effect of metformin combined with irradiation on A549 cells was detected by MTT. The migration and invasion capacity of tumor cells were assessed by wound healing assay and transwell chamber with matrigelgel,respectively. Expression of MMP- 2,MMP- 6,VEGF was measured by Western blot. Results MTT assay showed an obvious suppression of A549 cells proliferation in response to Metformin treatment. 12 h and 24 h migration distances in the metformin group,irradiation group and combined treatment group were lower than the control group. The combined treatment with metformin and Irradiation also caused a significantly higher inhibition rate of A549 cells invasion than metformin or Irradiate alone. The combined treatment group could down regulate the expression of VEGF,MMP- 9 and MMP- 2. Conclusion Metformin reduced the growth of lung cancer tumor cells,down regulated the expression of MMP- 2,MMP- 9 and VEGF,inhibited the lung cancer cell invasion. It suggests that metformin can play an important role in the metastasis of lung cancer and maybe a potential therapy for lung cancer.

关 键 词：二甲双胍 放疗 肺癌 侵袭 转移 

分 类 号：R734.2[医药卫生—肿瘤]