熊果酸通过HGF/c-met通路逆转肺癌A549细胞上皮间质转化及血管生成  

Ursolic acid reverses epithelial-mesenchymal transition and angiogenesis in lung cancer A549 cells through HGF/c-met pathway

作　　者：蔺晨[1] 李霜[1] 冯涛[1] 徐桂香[1] LIN Chen;LI Shuang;FENG Tao;XU Guixiang(Department of Respiratory and Critical Care Medicine,Shengli Oilfield Central Hospital,Shandong Dongying 257000,China)

机构地区：[1]胜利油田中心医院呼吸与危重症医学科,山东东营257000

出　　处：《现代肿瘤医学》2023年第12期2203-2208,共6页Journal of Modern Oncology

基　　金：山东省医药卫生科技发展计划项目(编号:202103020493)。

摘　　要：目的:探索熊果酸抑制由肝细胞生长因子(HGF)诱导肺癌细胞上皮间质转化(epithelial mesenchymal transition,EMT)及血管生成的作用机制研究。方法:利用CCK-8、侵袭实验、Western blot实验和小管形成实验研究熊果酸对HGF诱导的肺癌细胞增殖、细胞侵袭、EMT、管腔形成能力和相关信号通路分子表达的影响。结果:熊果酸能显著抑制肺癌A549细胞增殖,其作用肺癌A549细胞24 h的IC 50值为31.75μmol/L;HGF能使肺癌细胞穿透小室滤膜的数量显著增多(P<0.01),加入熊果酸作用后,肺癌细胞穿透小室滤膜的数量又显著降低(P<0.01);HGF能诱导肺癌EMT的形成(P<0.01),熊果酸则能抑制肺癌EMT形成(P<0.01);HGF能使小管形成明显增加(P<0.01),而熊果酸则能明显抑制小管的形成(P<0.01);此外,我们还研究了熊果酸对相关信号通路的影响,发现熊果酸能显著抑制HGF激活的HGF/c-met信号通路。同时,我们使用c-met抑制剂SU11274进一步研究其对肺癌细胞A549上皮间质转化及血管生成的影响,发现SU11274干预后和熊果酸具有相似的效应。结论:熊果酸抑制肺癌细胞的增殖、侵袭、EMT以及血管生成,其机制可能与HGF/c-met信号通路有关。Objective:To explore the mechanism of ursolic acid on epithelial-mesenchymal transition and angiogenesis in lung cancer cells induced by hepatocyte growth factor(HGF).Methods:The effect of ursolic acid(0,5,10,20,40,80μmol/L)on the proliferation of A549 cells were measured by CCK-8 assay.Transwell assay was used to determine the effect of ursolic acid on cell invasion.A549 cells were induced by HGF to establish EMT model,and the morphological changes of cells were observed under inverted microscope.The influence of ursolic acid on the angiogenesis of lung cancer was detected by the tube formation assay.The protein expression levels of E-cadherin,Vimentin and p-met were detected by Western blotting.Results:Ursolic acid significantly inhibited the proliferation of lung cancer A549 cells.IC 50 of ursolic acid(24 h)for the A549 cells was 31.75μmol/L.Ursolic acid significantly inhibited cell invasion and epithelial-mesenchymal transition of lung cancer A549 cells induced by HGF(P<0.01).Moreover,ursolic acid also inhibited HGF-induced angiogenesis of endothelial cells(P<0.01).In addition,molecular mechanism study showed that ursolic acid could inhibit HGF activated HGF/c-met signaling.At the same time,we used the c-met inhibitor SU11274 to further investigate its effects on epithelial-mesenchymal transition and angiogenesis in lung cancer A549 cells,and found that SU11274 had similar effects to ursolic acid.Conclusion:Ursolic acid inhibits proliferation,invasion,epithelial-mesenchymal transition and angiogenesis of lung cancer A549 cells,and the mechanism may be related to HGF/c-met signaling pathway.

关 键 词：熊果酸 HGF EMT 血管生成 

分 类 号：R734.2[医药卫生—肿瘤]