| Objectives:This study through the application of aldo keto reductase 1B10(AKR1B10)inhibitor combined with sorafenib in the treatment of hepatocellular carcinoma xenograft tumor models,and the efficacy was compared with that of sorafenib single drug to explore whether the AKR1B10 inhibitor could enhance the anti-hepatocellular carcinoma efficacy of sorafenib.Methods:1)HCC xenograft model:cell suspension was prepared by HepG2 cells 1.0×10~7/100?l(complete medium)and BD Matrigel 100?l,with a total volume of 0.2mL,which were implanted into the right armpit of nude mice.Mice were randomly divided into 4groups after a week,which were the control group(12),the epalrestat monotherapy group(14),the sorafenib monotherapy group(14)and combined treatment group(14)according to different interventions.2)Gavage for 2 weeks,the tumor volume was monitored regularly,the body weight of mice was monitored every day during the administration period and the weight of the isolated tumor tissue was measured.After two weeks of administration,tumor volume,tumor weight,T/C ratio and body weight of nude mice in each group were compared to evaluate the efficacy.The proliferation of tumor cells in each group was evaluated by comparing the positive rate of Ki-67.The number of TUNEL positive cells was used to evaluate the apoptosis of tumor cells among the groups.To evaluate whether AKR1B10 inhibitor combined with sorafenib can synergistically inhibit the growth of transplanted tumors in vivo.3)Statistical analysis of the data was performed using SPSS 19.0 software.The continuous variables were statistically described and statistically.The statistic was statistically described by mean±standard deviation((?)±s).One-way ANOVA was used for comparison among groups.LSD and Dunnett-t test were used for comparison between groups.The t-test was used to compare the two samples,and thec2 test was used between the multiple sample rates.The weight change of nude mice in each group was measured by repeated measures analysis of variance.P<0.05 was considered statistically significant.Results:Among the control group,epalrestat group,sorafenib group and combined therapy group,the tumor weights were 0.273±0.140,0.158±0.078,0.079±0.054,and 0.045±0.024(g),respectively,(F=16.594,P<0.001);the tumor volume differences before and after treatment were 238.940±39.813?124.991±84.670?-26.111±11.518?-54.072±17.673(mm~3),respectively,(F=37.048,P<0.001);the T/C ratios were 100%?58.9%?28.9%and 16.5%,respectively;Ki-67 positive rate were 23.295±6.218?13.503±3.392?7.325±2.257?4.664±1.189(%),respectively,(c~2=822.203,P<0.001).TUNEL positive rate were 6.902±2.224?9.889±2.024?23.225±4.046?28.916±5.485(%),respectively,(c~2=2435.849,P<0.001).Among them,the tumor volume differences before and after treatment(t=-3.579,P=0.002)and Ki-67 positive rate(t=-10.003,P<0.001)in the epalrestst monotherapy group were significantly lower than those in the control group,and TUNEL positive rate(t=3.367,P=0.003)were significantly higher than those in the control group.The tumor volume difference before and after treatment(t=2.056,P=0.025),tumor weight(t=2.101,P=0.043)and Ki-67 positive rate(t=-2.850,P=0.005)in the combined treatment group were significantly lower than those in the sorafenib monotherapy group,and TUNEL positive rate(t=6.370,P<0.001)were significantly higher than those in the sorafenib monotherapy group.Although the body weight of nude mice were decreased in both monotherapy groups and combined treatment group when comparing with the control group,there was no significant difference between epalrestat monotherapy group and the control group(t=-1.599,P=0.262),as well as sorafenib monotherapy group and the combination treatment group,during the course of treatment(t=-0.051,P=0.96).Conclusions:1.AKR1B10 inhibitor combined with sorafenib can synergistically inhibit the growth of HCC xenograft tumors;2.AKR1B10 inhibitor combined with sorafenib can inhibit the proliferation and promote apoptosis of HCC xenograft tumors. |
PDF Full Text Request