补中益气汤干预肺腺癌A549细胞移植瘤Wnt/β-catenin信号通路对顺铂敏感性的影响  

Effect of Buzhong Yiqi Decoction on the sensitivity of cisplatin by intervening Wnt/β-catenin signaling pathway in transplantation tumor of lung adenocarcinoma with A549 cells

作　　者：付权泽 牟琪瑞 刘春英[1] 王淳[1] 高原[1] FU Quan-Ze;MU Qi-Rui;LIU Chun-Ying(Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoning,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳110032

出　　处：《中国老年学杂志》2023年第8期1875-1879,共5页Chinese Journal of Gerontology

基　　金：国家自然科学基金资助项目(81403303,81973735,81774184);辽宁省教育厅面上项目(LJKZ0901)。

摘　　要：目的 探讨补中益气汤干预肺腺癌A549细胞移植瘤Wnt/β-catenin信号通路对顺铂敏感性的影响。方法 体外培养A549细胞,接种于BALB/cnu裸鼠腋窝皮下,8 d成瘤,隔天开始分别给予低剂量(1.46 g/kg)、中剂量(2.91 g/kg)、高剂量(5.82 g/kg)补中益气汤治疗25 d。30只裸鼠随机分为5组:对照组、顺铂组、顺铂+低剂量补中益气汤组、顺铂+中剂量补中益气汤组、顺铂+高剂量补中益气汤组。测量移植瘤质量并计算药物抑瘤率;Western印迹检测细胞质中p-糖原合成激酶(GSK)-3βser9、p-GSK-3βtyr216、GSK-3β蛋白的表达;实时荧光定量聚合酶链反应(PCR)和蛋白质印迹法检测移植瘤组织β-catenin、Survivin蛋白的表达。结果 给药25 d后,顺铂联合不同剂量补中益气汤使移植瘤质量均显著缩小(P<0.05),抑瘤率均显著增加(P<0.05),且呈剂量依赖性。与对照组相比,顺铂联合不同剂量补中益气汤组可显著下调移植瘤细胞质p-GSK-3βser9蛋白的表达(P<0.05),并显著下调β-catenin、Survivin mRNA和蛋白表达(P<0.05),尤以顺铂联合高剂量补中益气汤组效果最明显。结论 补中益气汤可通过抑制Wnt/β-catenin信号通路增强顺铂对肺腺癌的敏感性。Objective To explore the effect of Buzhong Yiqi Decoction on the sensitivity of cisplatin by intervening Wnt/β-catenin signaling pathway in transplantation tumor of lung adenocarcinoma with A549 cells.Methods A549 cells were cultured in vitro and inoculated subcutaneously into the axillary of BALB/cnu nude mice.The tumor was formed 8 d later.Low dose(1.46 g/kg),medium dose(2.91 g/kg)and high dose(5.82 g/kg)Buzhong Yiqi Decoction were given for 25 d from the next day.Thirty nude mice were randomly divided into 5 groups:control group,cisplatin group,cisplatin+low dose Buzhong Yiqi Decoction group,cisplatin+medium dose Buzhong Yiqi Decoction group and cisplatin+high dose Buzhong Yiqi Decoction group.The weight of transplantation tumor was measured and tumor inhibitory rate was calculated.Western blot was used to detect the expressions of p-glycogen synthetic kinase(p-GSK)-3βser9,p-GSK-3βtyr216 and GSK-3βprotein in the cytoplasm;real-time polymerase chain reaction(PCR)and Western blot were used to determine the expressions ofβ-catenin and Survivin protein in the tumor tissue.Results After 25 d of administration,cisplatin combined with different dose of Buzhong Yiqi Decoction significantly reduced the weight of transplantation tumor(P<0.05)and significantly increased the tumor inhibition rate(P<0.05),and it was dose-dependent.Compared with control group,cisplatin combined with different dose of Buzhong Yiqi Decoction significantly downregulated the expression of p-GSK-3βser9 protein in transplantion of tumor cytoplasm(P<0.05),and significantly downregulated the expressions ofβ-catenin,Survivin mRNA and protein(P<0.05),especially cisplatin combined with high-dose Buzhong Yiqi Decoction group had the best effect.Conclusions Buzhong Yiqi Decoction could enhance the sensitivity of cisplatin to lung adenocarcinoma by inhibiting Wnt/β-catenin signaling pathway.

关 键 词：补中益气汤 A549细胞株 顺铂 耐药 WNT/Β-CATENIN信号通路 

分 类 号：R365[医药卫生—病理学]