摘要
目的:通过对补中益气汤联合顺铂对肺腺癌荷瘤裸鼠移植瘤连环蛋白(β-catenin)mRNA及蛋白表达影响的研究,探讨补中益气汤改善肺癌顺铂耐药的分子机制。方法:培养A549、A549/DDP细胞,分别接种于裸鼠腋窝皮下,并将60只裸鼠随机分为10组,即A549/DDP荷瘤对照组(A组)、A549/DDP荷瘤+顺铂组(B组)、A549/DDP荷瘤+顺铂+低剂量补中益气汤组(C组)、A549/DDP荷瘤+顺铂+中剂量补中益气汤组(D组)、A549/DDP荷瘤+顺铂+高剂量补中益气汤组(E组)、A549荷瘤对照组(a组)、A549荷瘤+顺铂组(b组)、A549荷瘤+顺铂+低剂量补中益气汤组(c组)、A549荷瘤+顺铂+中剂量补中益气汤组(d组)、A549荷瘤+顺铂+高剂量补中益气汤组(e组),每组6只。接种后第8天成瘤,第9~25天给药,第25天处死,剥取移植瘤称质量,计算顺铂抑瘤率。Real-time PCR法和蛋白质印迹法分别测定荷瘤裸鼠移植瘤组织β-catenin mRNA和蛋白表达。结果:A549/DDP细胞荷瘤裸鼠各组中,C、D、E组较A、B组瘤质量显著下降(P<0.05);B组较A组移植瘤β-catenin mRNA和蛋白表达上调(P<0.05),而C、D、E组较B组β-catenin mRNA和蛋白的表达下调(P<0.05)。A549细胞荷瘤裸鼠各组中,b、c、d、e组较a组移植瘤质量显著减轻(P<0.05),c、d、e组较b组瘤质量进一步减轻(P<0.05);b、c、d、e组较a组移植瘤β-catenin mRNA和蛋白表达下调(P<0.05),d、e组较b组β-catenin mRNA和蛋白的表达进一步下调(P<0.05)。结论:补中益气汤改善肺癌顺铂耐药的机制可能与β-catenin的表达下调、抑制Wnt/β-catenin信号通路有关。
Objective:To explore the molecular mechanism of Buzhong Yiqi Decoction in improving cisplatin resistance in human lung cancer by investigating the effect of Buzhong Yiqi Decoction combined with Cisplatin on the expression ofβ-catenin mRNA and protein in human lung cancer transplantation tumor in nude mice.Methods:A549 and A549/DDP cells were cultured and inoculated subcutaneously in the armpit of nude mice,and sixty nude mice were randomly divided into 10 groups,six mice in each group.The groups were A549/DDP tumor-bearing control group(Group A),A549/DDP tumorbearing+Cisplatin(Group B),A549/DDP tumor-bearing+Cisplatin+low dose Buzhong Yiqi Decoction(Group C),A549/DDP tumor-bearing+Cisplatin+medium dose Buzhong Yiqi Decoction(Group D),A549/DDP tumor-bearing+Cisplatin+high dose Buzhong Yiqi Decoction(Group E),A549 tumor-bearing control group(Group a),A549 tumor-bearing+cisplatin(Group b),A549tumor-bearing+Cisplatin+low dose Buzhong Yiqi Decoction(Group c),A549 tumor-bearing+Cisplatin+medium dose Buzhong Yiqi Decoction(Group d),A549 tumor-bearing+Cisplatin+high dose Buzhong Yiqi Decoction(Group e).Tumor was formed on the 8th day after inoculation,the drugs wre administered on the 9th to 25th day,and all mice were killed after the 25th day.Then we peeled off the transplantation tumor and weighed them,calculated the tumor inhibition rate.The expression ofβ-catenin mRNA and protein was detected by Real-time PCR and Western blotting,respectively.Results:In A549/DDP tumor-bearing nude mice,The tumors’weight in Group C,D and E was significantly lower than that in Group A,B(P<0.05).The expression ofβ-catenin mRNA and protein was up-regulated in Group B compared with Group A(P<0.05),and the expression ofβ-catenin mRNA and protein in Group C,D and E was lower than that in Group B(P<0.05).In A549 tumor-bearing nude mice,the weight of transplantation tumors in Group b,c,d and e was significantly less than that in group a(P<0.05).Compared with Group b,the tumor weight of Group c,d and e decreased further(P<0.05).The expression ofβ-catenin mRNA and protein was lower in group b,c,d and e than that in Group a(P<0.05),the expression ofβ-catenin mRNA and protein was further down-regulated in Group d and e than in Group b(P<0.05).Conclusion:The mechanism of Buzhong Yiqi Decoction improving Cisplatin resistance may be related to down-regulation ofβ-catenin expression and inhibition of Wnt/β-catenin signal pathway.
作者
王莹
牟琪瑞
刘春英
高原
WANG Ying;MU Qi-rui;LIU Chun-ying;GAO Yuan(Department of Pathology,Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China;Graduate School,Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China)
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2022年第4期2191-2194,共4页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
国家自然科学基金项目(No.81403303,No.81973735)
辽宁省教育厅科研项目(No.LJKZ0901)。
