The inhibitory effect and mechanism of trastuzumab combined with clopidogrel tablets and bevaci-zumab on tumor proliferation in colorectal cancer mice
Objective To explore the inhibitory effect and mechanism of trafluridine pyrimidine tablets(TAS-102)combined with bevacizumab on tumor proliferation in colorectal Adenocarcinoma mice.Methods Sixty 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 in-jection 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 sacri-ficed 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 pro-tein A(Cyclin A)Expression levels of cell cycle protein E(Cyclin E),cyclin dependent kinase 4(CDK4),cyclin dependent kinase 6(CDK6).Results The 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[(6 833.82±821.95,7 958.06±994.61,5 021.38±633.52)vs.(13 625.67±1 182.42),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[(6 833.82±821.95)vs.(7 958.06±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 bevaci-zumab group[(1.64±0.14)vs.(2.10±0.32,6 833.82±821.95),t=5.136,6.742,P＜0.05],Tumor volume lower than TAS-102 group and bevacizumab group[(5 021.38±633.52 vs.(2.76±0.35,7 958.06±994.61),t=6.472,4.197,P＜0.05];The TGI of the combined intervention group was low-er than that of the TAS-102 group and the bevacizumab group[(66.93±5.68)vs.(55.72±4.82,40.80±3.25),t=4.178,6.032,P＜0.05].The expression of VEGF protein in TAS-102 group,bevaci-zumab group,and combined intervention group mice was lower than that in the control group[(0.63±0.10),(0.75±0.13),(0.45±0.11)vs.(1.00±0.08),t=3.052,4.102,2.573,P＜0.05],Flt-1 protein expression is lower than the control group[(0.56±0.09,0.68±0.10,0.39±0.10)vs.(1.00±0.08),t=2.763,4.982,3.362,P＜0.05];And the expression of VEGF and Flt-1 proteins in the TAS-102 group was lower than that in the control group[(0.63±0.10,0.56±0.09)vs.(1.00±0.08,1.00±0.10),t=4.712,3.516,P＜0.05];The VEGF and Flt-1 proteins in the combined inter-vention group were lower than those in the TAS-102 group[(0.45±0.11,0.39±0.10)vs.(0.63±0.10,0.56±0.09),t=4.032,3.154,P＜0.05]and Bevacizumab group[(0.45±0.11,0.39±0.10)vs.(0.75±0.13,0.68±0.10),t=4.358,5.921,P＜0.05].The protein expression of Cyclin A,Cyc-lin E,CDK4,and CDK6 in TAS-102 group mice was lower than that in the control group[(0.61±0.09,0.57±0.09,0.53±0.08,0.66±0.10)vs.(1.00±0.10,1.02±0.08,1.00±0.10,1.03±0.11),t=3.251,5.407,4.096,3.157,P＜0.05];The protein expression of Cyclin A,Cyclin E,CDK4,and CDK6 in the bevacizumab group was lower than that in the control group[(0.82±0.10,0.79±0.11,0.69±0.11,0.85±0.09)vs.(1.00±0.10,1.02±0.08,1.00±0.10,1.03±0.11),t=5.381,4.702,5.107,3.092,P＜0.05];The combined intervention resulted in lower protein expression of Cyc-lin A,Cyclin E,CDK4,and CDK6 compared to the control group[(0.33±0.07,0.40±0.08,0.35±0.09,0.42±0.07)vs.(1.00±0.10,1.02±0.08,1.00±0.10,1.03±0.11),t=5.892,4.219,4.031,3.175,P＜0.05];And the protein expression of Cyclin A,Cyclin E,CDK4,and CDK6 in the TAS-102 group was lower than that in the bevacizumab group[(0.61±0.09,0.57±0.09,0.53±0.08,0.66±0.10)vs.(0.82±0.10,0.79±0.11,0.69±0.11,0.85±0.09),t=4.762,5.321,3.073,4.054,P＜0.05];The protein expression of Cyclin A,Cyclin E,CDK4,and CDK6 in the combined in-tervention group was lower than that in the TAS-102 group[(0.33±0.07,0.79±0.11,0.35±0.09,0.42±0.07)vs.(0.61±0.09,0.57±0.09,0.53±0.08,0.66±0.10),t=3.175,5.321,3.073,P＜0.05]and Bevacizumab group[(0.33±0.07,0.79±0.11,0.35±0.09,0.42±0.07)vs.(0.82±0.10,0.79±0.11,0.69±0.11,0.85±0.09),t=4.081,5.732,4.193,P＜0.05].Conclusion TAS-102 combined with bevacizumab has a good inhibitory effect on tumor proliferation in colorectal cancer mice,and its mechanism is related to anti angiogenesis and regulation of cell cycle processes.
NETL
NSTL
万方数据
