血府逐瘀汤对裸鼠食管癌移植瘤的放射增敏作用及机制  

Radiosensitization Effect and Mechanism of Xuefu Zhuyutang on Transplanted Esophageal Carcinoma in Nude Mice

作　　者：陈乐君 黄腾 王逸君[1] 赵迪[1] 黄维[1] 马珺[1] 鹿红[1] 于大海[1] CHEN Le-jun;HUANG Teng;WANG Yi-jun;ZHAO Di;HUANG Wei;MA Jun;LU Hong;YU Da-hai(Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210029,China)

机构地区：[1]南京中医药大学附属医院,南京210029

出　　处：《中国实验方剂学杂志》2022年第9期23-28,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：江苏省中医药管理局科技项目(YB201815);江苏省研究生科研创新计划项目(KYCX21_1707);江苏省中医院科技项目(Y21022)。

摘　　要：目的:探讨血府逐瘀汤对食管癌皮下移植瘤放射增敏的可能作用机制。方法:建立人食管癌ECA-109裸鼠皮下移植瘤模型,将其随机分为模型组、单纯照射组、血府逐瘀汤组、联合组,每组6只。干预结束后剥除移植瘤并称量其质量,计算各组抑瘤率;然后用免疫组化法(IHC)检测缺氧诱导因子-1α(HIF-1α)、血管内皮生长因子A(VEGFA)蛋白表达,蛋白免疫印迹法(Western blot)检测移植瘤中人哺乳动物雷帕霉素靶蛋白(mTOR)、HIF-1α、VEGFA、血管内皮生长因子受体2(VEGFR2)蛋白表达;实时荧光定量聚合酶链式反应(Real-time PCR)检测移植瘤中mTOR、HIF-1α、VEGFA mRNA表达。结果:与模型组比较,单纯照射组、血府逐瘀汤组瘤质量明显下降(P<0.05),联合组瘤质量显著下降(P<0.01);与单纯照射组比较,联合组瘤体质量明显下降(P<0.05),该组抑瘤率达到57.37%;与模型组比较,单纯照射组、血府逐瘀汤组、联合组VEGFR2、p-mTOR、HIF-1α、VEGFA蛋白水平明显降低(P<0.05,P<0.01),单纯照射组、血府逐瘀汤组、联合组mTOR、HIF-1α,VEGFA mRNA水平明显降低(P<0.05,P<0.01);与单纯照射组比较,联合组VEGFR2、p-mTOR、HIF-1α、VEGFA蛋白表达明显下降(P<0.05,P<0.01),联合组mTOR、HIF-1α、VEGFA mRNA表达明显下降(P<0.05,P<0.01)。结论:血府逐瘀汤可以抑制食管癌ECA109裸鼠移植瘤的生长,与放疗联用具有明显的放射增敏作用,其机制可能与抑制mTOR/HIF-1α/VEGFA乏氧信号通路的表达相关。Objective:To explore the radiosensitization and underlying mechanism of Xuefu Zhuyutang on subcutaneous transplanted esophageal carcinoma.Method:The subcutaneous xenograft model of human esophageal carcinoma ECA-109 in nude mice was induced and the model mice were divided into a model group,an irradiation group,a Xuefu Zhuyutang group,and a combination group,with six nude mice in each group.After the intervention,the transplanted tumors were removed and weighed,and the tumor inhibition rate of each group was calculated according to the formula.The protein expression of hypoxia-inducible factor-1α(HIF-1α)and vascular endothelial growth factor A(VEGFA)was detected by immunohistochemistry(IHC).The protein expression of mammalian target of rapamycin(mTOR),HIF-1α,VEGFA,and vascular endothelial growth factor receptor 2(VEGFR2)in transplanted tumors was detected by Western blot.The mRNA expression of mTOR,HIF-1α,and VEGFA in transplanted tumors was detected by real-time quantitative polymerase chain reaction(Real-time PCR).Result:Compared with the conditions in the model group,the tumor weight decreased in the irradiation group and the Xuefu Zhuyutang group(P<0.05),as well as the combination group(P<0.01).Compared with the irradiation group,the combination group showed decreased tumor weight(P<0.05),with tumor inhibition rate of 57.37%.Compared with the model group,the irradiation group,the Xuefu Zhuyutang group,and the combination group showed decreased protein expression of VEGFR2,p-mTOR,HIF-1α,and VEGFA(P<0.05,P<0.01)and reduced mRNA expression of mTOR,HIF-1α,and VEGFA(P<0.05,P<0.01).Compared with the irradiation group,the combination group showed down-regulated protein expression of VEGFR2,p-mTOR,HIF-1α,and VEGFA(P<0.05,P<0.01)and reduced mRNA expression of mTOR,HIF-1α,and VEGFA(P<0.05,P<0.01).Conclusion:Xuefu Zhuyutang can inhibit the growth of transplanted esophageal carcinoma ECA-109 in nude mice and shows an obvious radiosensitization effect in combination with radiotherapy.The mechanism may be related t

关 键 词：食管癌 放射增敏 血府逐瘀汤 缺氧诱导因子-1Α 

分 类 号：R22[医药卫生—中医基础理论] R242[医药卫生—中医学]