补中益气汤联合顺铂对小鼠移植性肺癌增效减毒的协同作用研究  

Synergistic Attenuated Antitumor Effect of Buzhong Yiqi Decoction(补中益气汤)Combined with Cisplatin in Lewis Lung Tumor-Bearing Mice

作　　者：王洁 王辉[2] 戴灵豪[2] 王林燕[2] 王博[2] 陈亮[2] WANG Jie;WANG Hui;DAI Linghao;WANG Linyan;WANG Bo;CHEN Liang(Chinese Hospital of Changxing County,Huzhou,Zhejiang 313100;Zhejiang Chinese Medicine University,Hangzhou,Zhejiang 310053)

机构地区：[1]浙江省长兴县中医院,浙江湖州313100 [2]浙江中医药大学,浙江杭州310053

出　　处：《中国中医药科技》2020年第4期519-524,共6页Chinese Journal of Traditional Medical Science and Technology

基　　金：浙江省中医药科技计划项目(2017ZA041)。

摘　　要：目的:探讨补中益气汤联合顺铂对小鼠移植性肺癌增效减毒的协同作用。方法:建立Lewis肺癌细胞荷瘤小鼠模型,随机分为模型组、顺铂组、补中益气汤组、联合给药组,每组10只。各组给药22 d后解剖小鼠,称重瘤块质量计算抑瘤率,并在显微镜下计数肺转移瘤灶的个数;ELISA检测小鼠血清中IL-2、IL-10、IFN-γ、TNF-α的水平;流式细胞术检测小鼠外周血CD4^+CD25^+ Foxp3^+调节性T细胞(T regulatory cell,Treg)的表达比例;WB检测小鼠移植性肺癌细胞凋亡相关蛋白Bcl-2、Bax、p53、Fas、Fasl和耐药相关蛋白MRP1、ERCC1的表达情况。结果:与模型组相比,补中益气汤以及联合顺铂均能有效抑制肿瘤的生长和肺转移灶的数量(P<0.05)。补中益气汤、顺铂以及联合给药均能显著调节IL-2、IL-10、IFN-γ、TNF-α的表达水平,且联合组的IL-2、IL-10、TNF-α水平差异极显著(P<0.01)。流式分析结果显示各组给药后均能显著降低小鼠外周血CD4^+CD25^+ Foxp3^+Treg细胞比例,且联合给药组的降低效果最明显,与顺铂组相比差异显著(P<0.05)。WB结果显示补中益气汤、顺铂以及联合给药均能促进促凋亡相关蛋白Bax、p53、Fas、Fasl的表达,降低抑凋亡相关蛋白Bcl2的蛋白表达(P<0.05)。此外,与模型组相比,顺铂组的多药耐药相关蛋白MRP1、ERCC1的表达显著升高(P<0.05),而补中益气汤联合顺铂给药后能显著降低MRP1、ERCC1的蛋白表达(P<0.05)。结论:补中益气汤联合顺铂对Lewis肺癌细胞荷瘤小鼠抗肿瘤具有增效减毒的作用,其机制可能与调节细胞因子IL-2、IL-10、IFN-γ、TNF-α表达和Treg细胞比例,以及凋亡相关蛋白Bcl-2、Bax、p53、Fas、Fasl和耐药相关蛋白MRP1、ERCC1的表达有关。Objective:To observe the synergistic attenuated antitumor effect of Buzhong Yiqi Decoction(BZYQD)combined with cisplatin in Lewis lung tumor-bearing mice.Methods:After the model of Lewis lung cell was established,the nude mice were randomly divided in to model group,cisplatin group,BZYQD group,and combined group with each 10 rats.After 22 days of administration,tumor was isolated and weighted to evaluate the inhibition rate,and the number of lung metastases were also calculated.Flow cytometry was applied to evaluate the percentage of CD4^+CD25^+ Foxp3^+ Treg cells,ELISA assay was used to determine the serum level of IL-2,IL-10,IFN-γ,TNF-α,WB was performed to measure the protein content of Bcl-2,Bax,p53,Fas,Fasl,MRP1,ERCC1.Results:comparing with model group,the weight of tumor and number of lung metastases were also decreased significantly in cisplatin,BZYQD,and combined group(P<0.05).The serum levels of IL-2,IL-10,IFN-γ,TNF-αwere significantly decreased in cisplatin,BZYQD group(P<0.05)and combined group(P<0.01).Flow cytometry result showed that percentage of CD4^+CD25^+ Foxp3^+ Treg cells were significantly decreased in Cisplatin,BZYQD group(P<0.05)and combined group(P<0.01).WB results also indicated that the protein content of Bax,p53,Fas,Fasl can be increased and Bcl2 was inhibited in cisplatin,BZYQD,and combined group(P<0.05).And the expression of MRP1,ERCC were increased significantly with the administration of cisplatin,but BZYQD can significantly inhibit the elevated expression of MRP1and ERCC in combined group(P<0.05).Conclusion:BZYQD combined with cisplatin have the synergistic antitumor effect in Lewis tumor-bearing mice.The mechanism may relate to regulation the expressions of serum IL-2,IL-10,IFN-γ,TNF-α,Treg cells,and protein expressions of Bcl-2,Bax,p53,Fas、Fasl,MRP1、ERCC1.

关 键 词：肺癌 补中益气汤 顺铂 增效减毒 

分 类 号：R734.2[医药卫生—肿瘤]