曲氟尿苷替匹嘧啶片联合贝伐珠单抗对结直肠癌小鼠肿瘤增殖的抑制作用及其机制  

The inhibitory effect and mechanism of trastuzumab combined with clopidogrel tablets and bevacizumab on tumor proliferation in colorectal cancer mice

作　　者：俞彦文 曹晨曦 Yu Yanwen;Cao Chenxi(Jiaxing University Master Degree Cultivation Base,Zhejiang Chinese Medical University,Jiaxing 314000,China;Department of Gastroenterology,Second Affiliated Hospital of Jiaxing University,Jiaxing 314000 China)

机构地区：[1]浙江中医药大学嘉兴大学联培基地,嘉兴314000 [2]嘉兴大学附属第二医院胃肠外科,嘉兴314000

出　　处：《中华实验外科杂志》2024年第12期2773-2777,共5页Chinese Journal of Experimental Surgery

基　　金：嘉兴市科技计划项目(2023AD31039)。

摘　　要：目的探究曲氟尿苷替匹嘧啶片(TAS-102)联合贝伐珠单抗对结直肠腺癌小鼠肿瘤增殖的抑制作用及机制。方法 60只BALB/c裸鼠经采用皮下肿瘤接种法制备皮下结直肠腺癌肿瘤裸鼠模型后, 随机数字表分为4组, 各组15只, 对照组(不进行任何处理)、TAS-102组(第1~14天每天两次口服TAS-102, 每次75 mg/kg)、贝伐单抗组(每3天腹腔注射5 mg/kg贝伐珠单抗)、联合干预组(每天口服两次TAS-102, 每次75 mg/kg, 每3 d腹腔注射5 mg/kg贝伐珠单抗)。末次给药24 h后处死小鼠, 称量瘤组织重量, 计算肿瘤体积及肿瘤生长抑制比(TGI)。采用蛋白质印迹法(Western blot)实验测定血管内皮生长因子(VEGF)、血管内皮生长因子受体1(VEGFR-1/Flt-1)、细胞周期蛋白A(Cyclin A)、细胞周期蛋白E(Cyclin E)、周期蛋白依赖性激酶4(CDK4)、周期蛋白依赖性激酶6(CDK6)的表达水平。组间比较采用t检验。结果 TAS-102组、贝伐单抗组及联合干预组小鼠肿瘤重量低于对照组[(2.10±0.32、2.76±0.35、1.64±0.14)比(3.45±0.37), t=8.617, P<0.05]、肿瘤体积均低于对照组[(6 833.82±821.95、7 958.06±994.61、5 021.38±633.52)比(13 625.67±1 182.42), t=7.503, P<0.05];TAS-102组肿瘤重量低于贝伐单抗组[(2.10±0.32)比(2.76±0.35), t=6.357, P<0.05]、肿瘤体积低于贝伐单抗组[(6 833.82±821.95)比(7 958.06±994.61), t=5.015, P<0.05];联合干预组肿瘤重量低于TAS-102组和贝伐单抗组[(1.64±0.14)比(2.10±0.32、6833.82±821.95), t=5.136、6.742, P<0.05]、肿瘤体积低于TAS-102组及贝伐单抗组[(5 021.38±633.52)比(2.76±0.35、7 958.06±994.61), t=6.472、4.197, P<0.05];联合干预组TGI低于TAS-102组和贝伐单抗组[(66.93±5.68)比(55.72±4.82、40.80±3.25), t=4.178、6.032、P<0.05]。TAS-102组、贝伐单抗组及联合干预组小鼠VEGF蛋白表达低于对照组[(0.63±0.10、0.75±0.13、0.45±0.11)比(1.00±0.08), t=3.052、4.102、2.573, P<0.05]、Flt-1蛋白表达低于对照组[(0.56±0.09、0.68ObjectiveTo explore the inhibitory effect and mechanism of trafluridine pyrimidine tablets(TAS-102)combined with bevacizumab on tumor proliferation in colorectal Adenocarcinoma mice.MethodsSixty BALB/c nude mice were prepared with subcutaneous colorectal Adenocarcinoma cancer tumor model by subcutaneous tumor inoculation method,and were randomly divided into 4 groups with 15 mice in each group,which were named as follows:Control group(without any treatment),TAS-102 group(from day 1 to 14,oral TAS-102 twice a day,75 mg/kg each time),bevacizumab group(intrabitoneal injection of 5 mg/kg bevacizumab every 3 days),combined intervention group(oral TAS-102 twice a day,75 mg/kg each time),Intraperitoneal injection of 5 mg/kg bevacizumab every 3 days.The mice were sacrificed 24 hours after the last administration,the tumor tissue weight was weighed,the tumor volume and tumor growth inhibition ratio(TGI)were calculated.Western blotting assay was used to determine vascular endothelial growth factor(VEGF),vascular endothelial growth factor receptor-1(Flt-1)and cell cycle protein A(Cyclin A)Expression levels of cell cycle protein E(Cyclin E),cyclin dependent kinase 4(CDK4),cyclin dependent kinase 6(CDK6).ResultsThe tumor weight of mice in the TAS-102 group,bevacizumab group,and combined intervention group was lower than that of the control group[(2.10±0.32,2.76±0.35,1.64±0.14)vs.(3.45±0.37),t=8.617,P<0.05],the tumor volume was lower than that of the control group[(6833.82±821.95,7958.06±994.61,5021.38±633.52)vs.(13625.67±1182.42),t=7.503,P<0.05];The tumor weight in the TAS-102 group was lower than that in the bevacizumab group[(2.10±0.32)vs.(2.76±0.35),t=6.357,P<0.05],tumor volume lower than Bevacizumab group[(6833.82±821.95)vs.(7958.06±994.61),t=5.015,P<0.05];The tumor weight in the combined intervention group was lower than that in the TAS-102 group and bevacizumab group[(1.64±0.14)vs.(2.10±0.32,6833.82±821.95),t=5.136,6.742,P<0.05],Tumor volume lower than TAS-102 group and bevacizumab group[(5021.38±633.52)

关 键 词：结直肠癌 曲氟尿苷替匹嘧啶片 贝伐珠单抗 BALB/c小鼠 抗血管生成 

分 类 号：R965[医药卫生—药理学]