[AKR1B10 inhibitor enhances the inhibitory effect of sorafenib on liver cancer xenograft].

Objective: To investigate the inhibitory effect of AKR1B10 inhibitor combined with sorafenib on hepatocellular carcinoma (HCC) xenograft growth. Methods: HepG2 xenograft model was established in nude mice. The mice were then randomly divided into four groups: control group, epalrestat monotherapy group, sorafenib monotherapy group and combination treatment group. Tumor volume, tumor weight, T/C ratio and the change in body weight of nude mice in each group were compared to evaluate the curative effect. Immunohistochemistry staining was used to detect the expression of Ki-67 in tumor tissues to evaluate the proliferation status of tumor cells. One-way analysis of variance was used to compare the differences between the groups. Student's t-test was used to test means of two groups and chi-square test was used for multiple samples. Results: The differences of the grafted tumor volume before and after treatment between the control group, epalrestat group, sorafenib group and combined therapy group was 238.940 ± 39.813, 124.991 ± 84.670, -26.111 ± 11.518, and -54.072 ± 17.673(mm(3)), respectively, (F = 37.048, P < 0.001). The tumor mass were 0.273 ± 0.140, 0.158 ± 0.078, 0.079 ± 0.054, 0.045 ± 0.024 (g), (F = 16.594, P < 0.001); T/C ratio were 100%, 57.9%, 28.9%, 16.5%, and Ki-67 positive rate were 23.295 ± 6.218, 13.503 ± 3.392, 7.325 ± 2.257, 4.664 ± 1.189 (%), (χ(2) = 822.203, P < 0.001) . The tumor volume (t = -3.579, P = 0.002) and Ki-67 positive rate (t = -10.003, P < 0.001) in epalrestat monotherapy group were significantly lower than control group. The tumor volume (t = 2.056, P = 0.025), tumor mass (t = 2.101, P = 0.043), and Ki-67 positive rate (t = -2.850, P = 0.005) in combination treatment group were significantly lower than sorafenib monotherapy group. Compared with the control group, the body weight of nude mice in the treatment group decreased to a certain extent, but there was no statistically significant difference between epalrestat monotherapy group and control group (t = -1.599, P = 0.262), and combined therapy and sorafenib monotherapy group (t = -0.051, P = 0.96). Conclusion: AKR1B10 inhibitor enhanced the inhibitory effect of sorafenib on hepatocellular carcinoma xenograft.目的： 探讨AKR1B10抑制剂联合索拉非尼对小鼠肝癌异种移植瘤生长的抑制作用。 方法： 建立裸鼠HepG2肝癌细胞异种移植瘤模型，随机分为4组：对照组、依帕司他单药组、索拉非尼单药组、联合治疗组；比较各组瘤体体积、瘤体质量、给病组和对照组瘤体平均质量比值、裸鼠体质量变化情况评价疗效，免疫组织化学法检测瘤体组织中Ki-67的表达评估肿瘤细胞增殖情况。多组间比较采用单因素方差分析，两样本均数用t检验，多样本率用χ(2)检验。 结果： 治疗前后移植瘤体积差值在对照组、依帕司他单药、索拉非尼单药、联合治疗组分别为（238.940±39.813）mm(3)、（124.991±84.670）mm(3)、（-26.111±11.518）mm(3)、（-54.072±17.673）mm(3)，F = 37.048，P < 0.001；瘤体质量分别为（0.273±0.140）g、（0.158±0.078）g、（0.079±0.054）g、（0.045±0.024）g，F = 16.594，P < 0.001，差异均有统计学意义。给药组与对照组肿瘤平均质量比值分别为100%、57.9%、28.9%、16.5%。Ki-67阳性率分别为23.295%±6.218%、13.503%±3.392%、7.325%±2.257%、4.664%±1.189%，（χ(2) = 822.203，P < 0.001），差异有统计学意义。依帕司他单药组治疗前后瘤体体积差值（t = -3.579，P = 0.002）、Ki-67阳性率比较（t = -10.003，P < 0.001）明显低于对照组，差异均有统计学意义。联合治疗组治疗前后瘤体体积差值（t = 2.056，P = 0.025）、瘤体质量(t = 2.101，P = 0.043)、Ki-67阳性率（t = -2.850，P = 0.005）明显低于索拉非尼单药组，差异均有统计学意义。给药组与对照组相比，裸鼠体质量均有一定下降，但依帕司他组与对照组（t = -1.599，P = 0.262）、联合治疗与索拉非尼组（t = -0.051，P = 0.96）相比，体质量下降均无统计学意义。 结论： AKR1B10抑制剂可增强索拉非尼对肝癌异种移植瘤的抑制作用。.