[1]王理槐,孙银辉,张领兄,等.基于Wnt/β-catenin信号通路探讨血府逐瘀汤在非小细胞肺癌EGFR-TKI获得性耐药中的作用[J].陕西中医,2022,(4):427-431.[doi:DOI:10.3969/j.issn.1000-7369.2022.04.004]
　WANG Lihuai,SUN Yinhui,ZHANG Lingxiong,et al.Efficacy of Xuefu Zhuyu decoction in EGFR-TKI-Acquired resistance of non-small cell lung carcinoma based on the Wnt/β-catenin signaling pathway[J].,2022,(4):427-431.[doi:DOI:10.3969/j.issn.1000-7369.2022.04.004]
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基于Wnt/β-catenin信号通路探讨血府逐瘀汤在非小细胞肺癌EGFR-TKI获得性耐药中的作用
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《陕西中医》[ISSN:1000-7369/CN:61-1281/TN]

卷:
期数:
2022年4期
页码:
427-431
栏目:
基础研究
出版日期:
2022-04-05

文章信息/Info

Title:
Efficacy of Xuefu Zhuyu decoction in EGFR-TKI-Acquired resistance of non-small cell lung carcinoma based on the Wnt/β-catenin signaling pathway
作者:
王理槐1; 孙银辉2 ; 张领兄3; 刘 欢2 ; 周 琴2; 袁苏云2; 张亚茹2; 朱 乐2 ; 张 红1
(1.湖南中医药大学第一附属医院,湖南 长沙 410007; 2.湖南中医药大学,湖南 长沙 410208; 3.重庆市九龙坡区中医院,重庆 400051)
Author(s):
WANG Lihuai; SUN Yinhui; ZHANG Lingxiong; LIU Huan; ZHOU Qin; YUAN Suyun;  ZHANG Yaru; ZHU Le; ZHANG Hong
(The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine,Changsha 410007,China)
关键词:
非小细胞肺癌;  血府逐瘀汤;  表皮生长因子;  酪氨酸酶抑制剂;  获得性耐药;  Wnt/β-catenin信号通路
Keywords:
Non-small cell lung carcinoma;  Xuefu Zhuyu decoction;  Epidermal growth factor receptor;  Tyrosine kinase inhibitor;  Acquired drug resistance;  Wnt/β-catenin signaling pathway
分类号:
R 734.2
DOI:
DOI:10.3969/j.issn.1000-7369.2022.04.004
文献标志码:
A
摘要:
目的:探讨血府逐瘀汤基于Wnt/β-catenin信号通路对非小细胞肺癌(NSCLC)表皮生长因子(EGFR)-酪氨酸酶抑制剂(TKI)获得性耐药小鼠模型的干预作用。方法:选取SPF级Balb/c小鼠40只,腋下接种NSCLC EGFR-TKI获得性耐药细胞株构建皮下移植瘤,随机分为空白组、TKI组、低剂量组、高剂量组、高剂量+TKI组,共五组,每组8只。各组小鼠均经灌胃给药,给药剂量:厄洛替尼(TKI)30 mg/(kg·d),血府逐瘀汤低剂量含生药15 mg/ml、30 ml/(kg·d)给药,高剂量含生药45 mg/ml、30 ml/(kg·d)给药。空白组给予0.9%氯化钠溶液(0.4 ml/只)。比较各组瘤体体积、肿瘤生长抑制率、肿瘤细胞增殖指数、Wnt3α、P-GSK3β与β-catenin的蛋白表达情况。结果:在给药第16天、第20天时,高剂量+TKI组瘤体体积小于空白组及TKI组,在给药第20天时,高剂量组瘤体体积小于空白组(P<0.05)。在给药第16天、第20天时,高剂量+TKI组瘤体生长抑制率高于TKI组、高剂量组,在给药第20天时,高剂量组瘤体生长抑制率高于TKI组(P<0.05)。空白组、TKI组、低剂量组肿瘤细胞增殖Ki67指数比较差异无统计学意义(P>0.05); 高剂量组、高剂量+TKI组肿瘤增殖Ki67指数均低于空白组,高剂量+TKI组肿瘤增殖Ki67指数低于高剂量组(P<0.05)。空白组、TKI组、低剂量组Wnt3α、P-GSK3β与β-catenin的蛋白表达比较差异无统计学意义(P>0.05); 高剂量组、高剂量+TKI组Wnt3α、β-catenin蛋白表达均低于空白组,P-GSK3β蛋白表达均高于空白组(P<0.05)。结论:高剂量血府逐瘀汤可抑制Wnt/β-catenin信号通路的激活,通过下调Wnt3α、β-catenin蛋白表达,上调P-GSK3β蛋白表达来延缓EGFR-TKI获得性耐药NSCLC小鼠肿瘤进展,抑制腋下移植瘤体积,降低肿瘤细胞增殖指数。
Abstract:
Objective:To explore the effect of Xuefu Zhuyu decoction on non-small cell lung carcinoma(NSCLC)with epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitor(TKI)acquired resistance mouse model based on Wnt/β-catenin signaling pathway.Methods:Forty SPF Balb/c mice were selected and inoculated with NSCLC EGFR-TKI-derived drug-resistant cell lines to construct subcutaneous xenografts.They were randomly divided into the blank group(n=8),the TKI group(n=8),the low-dose group(n=8),the high-dose group(n=8),and the high-dose +TKI group(n=8),5 groups in total.Mice in each group were administered intragastrically.The dosage:TKI(erlotinib)was given at 30 mg/(kg·d),Xuefu Zhuyu decoction containing crude drug 15 mg/ml in the low-dose group and 45 mg/ml in the high-dose group was given at 30 ml/(kg·d).The blank group was given 0.9% sodium chloride solution(0.4 ml/head).The tumor volume,tumor growth inhibition rate,tumor cell proliferation index,Wnt3α,P-GSK3-β and β-catenin protein expression were compared in each group.Results:On the 16th and 20th day,the tumor volume of the high-dose + TKI group was smaller than that of the blank group and the TKI group.On the 20th day,the tumor volume of the high-dose group was smaller than that of the blank group(P<0.05).On the 16th and 20th day,the tumor growth inhibition rate of the high-dose + TKI group was higher than that of the TKI group and the high-dose group.On the 20th day,the tumor growth inhibition rate of the high-dose group was higher than that of the TKI group(P<0.05).The Ki67 index of tumor proliferation in the blank group,TKI group and low-dose group was not statistically different(P>0.05).The Ki67 index of tumor proliferation in the high-dose group and the high-dose + TKI group was lower than that in the blank group,and the Ki67 index of tumor proliferation in the high-dose + TKI group was lower than that in the high-dose group(P<0.05).There was no significant difference in the protein expression of Wnt3α,P-GSK3β and β-catenin in the blank group,TKI group,and low-dose group(P>0.05).In the high-dose group and the high-dose + TKI group,the expression of wnt3α and β-catenin protein were lower than those in the blank group,the expression of P-GSK3β protein was higher than that in the blank group(P<0.05).Conclusion:High-dose Xuefu Zhuyu decoction can delay the tumor development,inhibit the size of transplanted tumor in the armpit and reduce the proliferation index of tumor cells of EGFR-TKI-acquired drug-resistant NSCLC mice by inhibiting the activation of Wnt/β-catenin signaling pathway,down-regulating the expression of Wnt3α and β-catenin protein and up-regulating the expression of P-GSK3β protein.

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备注/Memo

备注/Memo:
基金项目:湖南省自然科学基金资助项目(2020JJ4485)
更新日期/Last Update: 2022-04-08