目的：探讨二甲双胍对肿瘤血管及胃癌细胞生长的抑制作用。方法利用人脐静脉血管内皮细胞(HU-VEC)细胞划痕试验、Transwell侵袭实验、Matrigel血管状结构形成实验，研究二甲双胍对血管内皮细胞侵袭、迁移及血管状结构形成的影响，且运用流式细胞仪检测二甲双胍对血管内皮生长因子(VEGF)表达的影响；利用胃癌细胞BGC823的MTT实验、苏木精凋亡染色、Annexin-吁细胞凋亡实验、定量PCR凋亡因子检测实验，研究二甲双胍对胃癌细胞增殖、凋亡的影响。结果二甲双胍能够明显抑制HUVEC的迁移、侵袭、血管状结构形成，并且明显减少细胞VEGF的表达；二甲双胍对胃癌BGC823细胞的增殖有明显的抑制作用，且具有浓度依赖性，其中最大抑制率为68.80%，半抑制浓度(IC50)为(11.97±1.84)mmol/L；二甲双胍可以诱导胃癌BGC823细胞凋亡，具有浓度依赖性，10 mmol/L二甲双胍组凋亡比例接近60%；二甲双胍组BGC823细胞的Bcl-2 mRNA减少，而AMP-Kα1、Bax、Bad mRNA的表达增加。结论二甲双胍能够抑制肿瘤血管形成和胃癌细胞增殖，并诱导胃癌细胞凋亡，发挥抗胃癌细胞生长作用。%Objective To investigate the inhibiting effect of Metformin on the tumor angiogenesis and gastric cancer cell growth. Methods The cell scratch test, Transwell invasion assay and Matrigel vascular structure formation experi-ment of human umbilical vein endothelial cells (HUVEC) were used to study the effect of Metformin on vascular en-dothelial cell migration, invasion and the vascular structure formation, and the influence of Metformin on VEGF ex-pression was illuminated by flow cytometry; then MTT assay, hematoxylin apoptosis of dyeing, Annexin-Ⅴ apoptosis and quantitative PCR detection for apoptosis factors of gastric cancer BGC823 cells were conducted to research the ef-fect of Metformin on gastric cancer cell proliferation and apoptosis. Results Metformin could significantly inhibit en-dothelial cell migration, invasion, vascular structure of HUVEC, and reduce VEGF expression; Metformin had an obvi-ous inhibiting effect in gastric cancer BGC823 cells proliferation, with the concentration-dependence, the biggest inhi-bition rate was 68.80%, the 50% inhibiting concentration (IC50) was (11.97±1.84) mmol/L; Metformin could also in-crease cell apoptosis of BGC823 cells, with the concentration-dependence, the apoptosis rate of 10 mmol/L Metformin was close to 60%; the Bcl-2 mRNA of BGC823 cells treated by Metformin decreased, and the expression of AMPKα1, Bax, Bad mRNA increased. Conclusion Metformin can inhibit gastric cancer growth by inhibiting tumor angiogenesis and gastric cancer cell proliferation, and inducing gastric cancer apoptosis, which plays a role of inhibiting gastric can-cer cell growth.
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