AKR1B10 inhibitor enhances the inhibitory effect of sorafenib on liver cancer xenograft
10.3760/cma.j.issn.1007-3418.2019.01.009
- VernacularTitle: AKR1B10抑制剂增强索拉非尼对小鼠肝癌异种移植瘤的抑制作用
- Author:
Yuanyuan JIN
1
;
Chao HAN
;
Nan GENG
;
Yurong LI
;
Leyu ZHENG
;
Weijia ZHU
;
Yanwei LI
;
Ziying AN
;
Lianrong ZHAO
;
Jingyan WANG
;
Xiaoguang DOU
;
Han BAI
Author Information
1. Department of Infectious Disease, Shengjing Hospital of China Medical University, Shenyang 110022, China
- Publication Type:Journal Article
- Keywords:
Carcinoma, hepatocellular;
Hepatocellular carcinoma xenograft;
Aldo-keto reductase 1B10;
Epalrestat;
Sorafenib;
Combined treatment
- From:
Chinese Journal of Hepatology
2019;27(1):39-44
- CountryChina
- Language:Chinese
-
Abstract:
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(mm3), 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 (%), (χ2 = 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.
