Study of effect of four-and-a-half LIM protein 1 on paclitaxel-resistant in human hepatoma cell
10.13699/j.cnki.1001-6821.2017.12.018
- VernacularTitle:四个半LIM结构域蛋白1对人肝癌细胞紫杉醇耐药影响的研究
- Author:
Lei ZHOU
1
;
Ni JIANG
;
Xin-Na ZHOU
;
Xiao-Li WANG
;
Jun REN
Author Information
1. 首都医科大学附属北京世纪坛医院肿瘤内科
- Keywords:
paclitaxel;
hepatocellular carcinoma cell;
drug resistance;
four-and-a-half LIM protein 1
- From:
The Chinese Journal of Clinical Pharmacology
2017;33(12):1135-1138
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanisms of four and a half LIM protein 1 (FHL1) on paclitaxel resistance of hepatocellular carcinoma cells.Methods According to the expression of FHL1,two groups were set up:test group (hepatocellular carcinoma cell lines with knockdown of FHL-1) and control group (hepatocellular carcinoma cell lines expressing FHL-1).Both groups were treated with paclitaxel.In addition,oxaliplatin was used as a reference experiment.The antitumor effects of paclitaxel were detected by in vitro activity assay.The effects of paclitaxel on cell colony formation were analyzed by colony formation assay.The cell clones of both test group and contol group were inoculated in nude mice and then treated with paclitaxel.The situation of tumor growth and the effect of paclitaxel were observed.Meanwhile,the activity of Caspase-3 was determinated.Results The cell activity of the test group and the control group (HepG2 cells) was 0.41 ±0.02 and 0.70 ±0.02,respectively.The cell activity of the test group and the control group (SMMC 7721 cells) was 0.44 ± 0.02 and 0.63 ± 0.03,respectively.The difference was statistically significant.There was no significant difference in cell activity after the treatment of oxaliplatin(P ＞0.05).In cell colony formation,the numbers of clone formation were 93.52 ± 14.58 and 302.48 ±21.56 in HepG2 ceils.The numbers of clone formation were 55.14 ± 10.82 and 192.28 ± 19.47 in SMMC cells.The difference was statistically significant(P ＜ 0.05).There was no significant difference in cell activity after the treatment of oxaliplatin (P ＞ 0.05).In xenograft test,the tumor volume of the test group and the control group was 0.02 ± 0.02 and 1.89 ±0.51,respectively.The difference was statistically significant (P ＜ 0.05).Besides,the expression of Caspase-3 in the test group and the control group was 10.27 ± 0.47 and 26.72 ± 0.54,respectively.The difference was statistically significant (P ＜ 0.05).After being treated by the inhibitor of Caspase-3 (z-VAD-FMK),the expression of Caspase-3 in the test group and the control group was 8.87 ± 0.36 and 29.96 ± 0.68,respectively.The difference was statistically significant (P ＜ 0.05).Conclusion FHL1 is a paclitaxel resistance gene.After knockdown of FHL1,the antitumor effect of paclitaxel will be enhanced.Meanwhile,the activation of Caspase-3 is promoted,causing apoptosis induced by paclitaxel.
