大气细颗粒物PM2.5对肺癌血管新生的影响

Effect of PM2.5 Induced Angiogenesis in Lung Cancer

[目的]研究大气细颗粒物2.5(particulate matter2.5,PM2.5)对肺癌血管新生的影响。[方法]采集杭州大气PM2.5全颗粒物,对肺癌细胞A549进行染毒,CCK-8法观察PM2.5对肺癌A549细胞增殖的影响,选择50、100、150μg·m L^(-1)浓度的PM2.5染毒A549细胞24h,实时荧光定量PCR和Western blot检测血管内皮生长因子(vascular endothelial growth factor,VEGF)、基质金属蛋白酶-9(matrix metal proteinase-9,MMP-9)和缺氧诱导因子-1α(hypoxia-inducible factor-1α,HIF-1α)的m RNA和蛋白的表达。并建立人肺癌鸡胚移植瘤模型,用50、100、150μg·m L^(-1)的PM2.5染毒液处理肺癌移植瘤,测定PM2.5对血管数目和血管面积比值的影响。[结果]大于等于50μg·m 的PM2.5染毒后能促进A549细胞的增殖作用。与对照组比,PM2.5染毒A549细胞24h后VEGF、MMP-9与HIF-1α的m RNA和蛋白表达增加,并具有一定的量效关系。PM2.5染毒后肺癌鸡胚移植瘤模型新生血管数目和面积比高于对照组,差异有统计学意义(P<0.05,P<0.01)。[结论]PM2.5暴露能诱导肺癌中VEGF、MMP-9和HIF-1α基因的过表达,促进肺癌的血管新生,进而促使肺癌的发展。

[Objective] To explore the effects of PM2.5 on angiogenesis of human lung cancer. [Methods] The cultured human lung cancer cells A549 were exposed to 50,100,150 μg·m L-1PM2.5 for 24 hours, The PM2.5 callected in Hangzhou expose lung cancer line A549, VEGF, MMP-9 and HIF-1 α m RNA and protein expression in PM2.5-induced cells was assayed by Real-Time PCR and Western Blot. Then the A549 cell line was inoculated to the CAM to establish chicken embryo transplantion model of lung cancer, the transplanted tumors dealt with 50,100,150 μg·m L-1PM2.5, and the number of blood vessels and the ratio between vascular and CAM area were determined. [Results] PM2.5 stimulated the proliferation of A549 cells when the concentrations of PM2.5were higher than or equal to 50 μg·m L-1. The expression VEGF, MMP-9 and HIF-1α was promoted by PM2.5 with a concentration dependent manner. The number and area of new blood vessels in CAM transplantation tumor model were significantly higher than that of the control group（ P〈0.05,P〈0.01）.[Conclusion] PM2.5 exposure can induce overexpression of MMP-9, HIF-1α and VEGF in lung cancer, and promote tumor angiogenesis and the development of lung cancer.