加味龟鹿二仙胶汤对肺癌耐药裸鼠化疗药敏性的改善作用  

Effects of modified Guilu Erxianjiao Decoction in improving chemosensitivity resistance in nude mice with resistance to lung cancer

作　　者：师林[1] 黄圆圆[2] 柯斌 SHI Lin;HUANG Yuan-yuan;KE Bin(Department of Traditional Chinese Medicine,Zhujiang Hospital of Southern Medical University,Guangzhou 510282,China;Department of Traditional Chinese Medicine,Sun Yat-sen University Cancer Center,Guangzhou 510060,China)

机构地区：[1]南方医科大学珠江医院中医科,广东广州510282 [2]中山大学肿瘤防治中心中医科,广东广州510060

出　　处：《中成药》2021年第11期2976-2981,共6页Chinese Traditional Patent Medicine

基　　金：国家自然科学基金(81403300,81774175,81874381);广东省自然科学基金(2018A0303130121,2021A1515010491)。

摘　　要：目的观察加味龟鹿二仙胶汤通过IL-7介导的JAK3/STAT5信号通路对肺癌耐药裸鼠化疗药敏性的影响。方法建立气阴两虚型肺癌耐药裸鼠模型,分为正常对照组(不造模)、模型组(生理盐水)、顺铂组(顺铂)、中药组(加味龟鹿二仙胶汤)、联合组(加味龟鹿二仙胶汤+顺铂),每组10只,分别给予相应药,干预21 d。观察裸鼠一般情况,计算脾脏指数、抑瘤率,流式细胞仪检测CD4^(+)CD25^(+)Treg细胞,ELISA法检测血清中细胞因子IL-7水平,RT-qPCR检测肿瘤组织中耐药相关基因(P-gp、MRP 1)的表达,Western blot检测肿瘤组织中JAK3/STAT5信号通路的蛋白表达。结果中药组及联合组摄食量增加,精神状态较好,反应灵敏,体质量增加。联合组脾脏指数较模型组和顺铂组升高(P<0.05)。联合组抑瘤率较顺铂组升高(P<0.01),抑瘤率达70.12%。中药组、联合组CD4^(+)CD25^(+)Treg细胞比例均低于模型组(P<0.01)。模型组IL-7较正常对照组降低(P<0.01);中药组、联合组IL-7较顺铂组升高(P<0.01)。与顺铂组比较,中药组、联合组P-gp、MRP 1基因表达降低(P<0.05,P<0.01),p-JAK3、p-STAT5蛋白表达降低(P<0.01)。结论加味龟鹿二仙胶汤能抑制肿瘤生长,提高脾脏指数,纠正CD4^(+)CD25^(+)Treg细胞比例,解除机体免疫抑制状态,促进机体产生IL-7,调节IL-7介导的JAK3/STAT5信号通路,减少肺癌组织中耐药相关基因的表达,显著提升肺癌耐药裸鼠的免疫功能,从而改善肺癌顺铂化疗耐药。AIM To observe the effects of modified Guilu Erxianjiao Decoction on the chemotherapeutic sensitivity of nude mice with lung cancer resistant to chemotherapy via IL-7-mediated JAK3/STAT5 signal pathway.METHODS A drug-resistant nude mouse model of lung cancer with deficiency of both Qi and Yin was established.During the 21-day interventions,nude mice assigned into normal control group(no modeling),model group(saline solution),cisplatin group(cisplatin),traditional Chinese medicine(TCM)group(modified Guilu Erxianjiao Decoction),and combination group(modified Guilu Erxianjiao decoction+cisplatin)were treated accordingly,and general condition observed,their spleen index level and tumor inhibition rate calculated,their CD4^(+)CD25^(+)Treg cells detected by flow cytometry,their serum level of cytokine IL-7 detected by ELISA,their expressions of drug resistance-related genes(P-gp,MRP 1)in tumor tissues.investigated by RT-qPCR,their protein expressions of JAK3/STAT5 signal pathway in tumor tissues determined by Western blot.RESULTS The TCM group and the combination group shared increased food intake,better mental state,sensitive response,and increased body weight.The combination group showed its superiorities in the spleen index level than the model group and the cisplatin group(P<0.01),in tumor inhibition rate than the cisplatin group(P<0.01),in addition to the high tumor inhibition rate of 70.12%.The TCM group and the combination group displayed lower ratio of CD4^(+)CD25^(+)Treg cells than the model group(P<0.01).Lower IL-7 level in the model group than that in the normal control(P<0.01),and higher IL-7 in the TCM group and the combination group than that in the cisplatin group(P<0.01)were observed.Compared with the cisplatin group,both the TCM group and the combination group shared reduced expressions of P-gp and MRP 1 genes(P<0.05,P<0.01),and lower protein expressions of p-JAK3 and p-STAT5(P<0.01).CONCLUSION Modified Guilu Erxianjiao Decoction significantly improves the immune function of lung cancer mice,inhibits t

关 键 词：加味龟鹿二仙胶汤 非小细胞肺癌 化疗药敏性 JAK3/STAT5信号通路 顺铂化疗 

分 类 号：R285.5[医药卫生—中药学]