白桦脂酸通过抑制TGF-β2抑制A2780卵巢癌细胞上皮间质转化  

Betulinic acid inhibits epithelial-mesenchymal transition in A2780 ovarian cancer cells by suppressing TGF-β2

作　　者：黄岳[1] 张翔 庞学成 高洁凡[1] 颜利求[3] Huang Yue;Zhang Xiang;Pang Xuecheng;Gao Jiefan;Yan Liqiu(Department of Reproductive Medicine,Cangzhou Central Hospital,Cangzhou 061000,China;Cangzhou Central Hospital,Cangzhou 061000,China;Department of Cardiovascular Medicine,Cangzhou Central Hospital,Cangzhou 061000,China)

机构地区：[1]沧州市中心医院生殖医学科,沧州061000 [2]沧州市中心医院妇二科,沧州061000 [3]沧州市中心医院心血管内科,沧州061000

出　　处：《解剖学杂志》2025年第1期28-33,共6页Chinese Journal of Anatomy

基　　金：河北省重点研发计划项目(172777163)。

摘　　要：目的 :探讨白桦脂酸(BA)对卵巢癌A2780细胞上皮间质转化(EMT)的影响及机制。方法 :CCK-8检测不同浓度白桦脂酸处理A2780细胞24 h对A2780细胞活力的影响;选择0、5、10、20μmol/L白桦脂酸浓度处理24 h,检测白桦脂酸对A2780细胞EMT的影响;通过Oncomine预测参与卵巢癌的转化生长因子β(TGF-β)亚型;0、5、10、20μmol/L白桦脂酸处理A2780细胞24 h,检测TGF-β2的mRNA水平;将A2780细胞分为对照组、10μmol/L BA组、10μmol/LBA组+2ng/mL TGF-β2组,检测TGF-β2的加入是否能逆转白桦脂酸对A2780细胞EMT、侵袭迁移和耐药性的影响。结果 :白桦脂酸降低A2780的细胞活力,其IC50约为37.8μmol/L。与0μmol/L组相比,10μmol/L组和20μmol/L组白桦脂酸显著升高E-cadherin、降低N-cadherin、Vimentin蛋白表达水平。Oncomine预测显示TGF-β2在卵巢癌和正常组织中DNA拷贝数和mRNA表达差异较为明显。与0μmol/L组比,5、10、20μmol/L组白桦脂酸显著降低TGF-β2水平。与白桦脂酸10μmol/L组相比,10μmol/L BA组+2 ng/mL TGF-β2组降低E-cadherin蛋白表达;升高N-cadherin、Vimentin、基质金属蛋白酶(MMP)2、MMP-9、Smad2、Smad3的蛋白表达;增加侵袭细胞数,提高划痕愈合率和顺铂处理细胞的活力。结论 :白桦脂酸可能通过抑制TGF-β2相关EMT信号发挥抗肿瘤作用,降低卵巢癌A2780细胞的侵袭迁移和耐药性。Objective:To investigate the effect and mechanism of betulinic acid(BA)on epithelial-mesenchymal transition(EMT)in A2780 ovarian cancer cells.Methods:The viability of A2780 cells treated with different concentrations of betulinic acid(5–80μmol/L)for 24 hours was assessed by using the CCK-8 assay.The effects of BA on epithelial-mesenchymal transformation were detected under treatment with 0,5,10,20μmol/L of BA for 24 h.The transforming growth factor-β(TGF-β)subtype involved in ovarian cancer was predicted by Oncomine,and the mRNA levels of TGF-β2 in A2780 cells treated with BA(0,5,10,20µmol/L)for 24 hours were measured.A2780 cells were divided into control group,10μmol/L BA group,and 10μmol/L BA+2 ng/mL TGF-β2 group to determine whether TGF-β2 could reverse the effect of BA on epithelial mesenchymal transformation,invasion,migration and drug resistance in A2780 cells.Results:BA decreased the cell viability of A2780 with an IC50 of 37.8μmol/L.Compared with 0μmol/L BA group,the expression of E-cadherin was increased,while N-cadherin,Vimentin were significantly decreased in the 10μmol/L and 20μmol/L BA groups.Oncomine prediction results showed significant differences in both DNA copy numbers and mRNA expression levels of TGF-β2 between ovarian cancer and normal tissue.Compared with 0μmol/L BA group,the expression of TGF-β2 were significantly decreased in the 5,10,20μmol/L BA groups.Compared with the 10μmol/L BA group,the 10μmol/L BA+2 ng/mL TGF-β2 group had decreased E-cadherin,increased protein expression of N-cadherin,Vimentin,MMP-2,MMP-9,Smad2,Smad3,along with increased number of invaded cells,enhanced wound healing rate,and improved viability of cisplatin-treated cells.Conclusion:BA may exert its anti-tumor effects by inhibiting the TGF-β2-associated EMT signaling,thereby reducing the invasion,migration,and drug resistance of A2780 ovarian cancer cells.

关 键 词：白桦脂酸 卵巢癌 转化生长因子Β 上皮间质转化 转移 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]