文献类型：期刊文献

英文题名：Effects of the combination of As2O3 and AZT on proliferation inhibition and apoptosis induction of hepatoma HepG2 cells following silencing of Egr-1

作者：Zhao, Chuan[1];Wang, Mei[1];Liu, Yu[1];Liang, Yongjuan[1];Han, Li[2];Chen, Che[1]

第一作者：Zhao, Chuan

通信作者：Chen, C[1]

机构：[1]Gansu Univ Chinese Med, Clin Med Coll, Dept Clin Lab Diagnost & Mol Biol, 35 Dingxi East Rd, Lanzhou 730000, Gansu, Peoples R China;[2]Lanzhou Univ, Hosp 2, Emergency Res Inst, Lanzhou, Gansu, Peoples R China

第一机构：甘肃中医药大学临床医学院

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Clin Med Coll, Dept Clin Lab Diagnost & Mol Biol, 35 Dingxi East Rd, Lanzhou 730000, Gansu, Peoples R China.|[10735c1ddf597548aedb5]甘肃中医药大学临床医学院;[10735]甘肃中医药大学;

年份：2018

卷号：11

起止页码：3293

外文期刊名：ONCOTARGETS AND THERAPY

收录：;Scopus(收录号：2-s2.0-85047967165);WOS:【SCI-EXPANDED(收录号:WOS:000434027200003)】；

基金：This study was supported by National Natural Science Foundation of China (number 81460456) and Natural Science Foundation of Gansu Province (number 1308RJZA169).

语种：英文

外文关键词：HepG2; As2O3; AZT; Egr-1; proliferation; apoptosis

摘要：Context: Previous studies have demonstrated that 3'-azido-3'-deoxythymidine (AZT) and arsenic trioxide (As2O3), traditional chemotherapy agents, can synergically inhibit the growth of hepatocellular carcinoma cells. However, the molecular mechanisms underlying As2O3 and AZT anti-hepatoma activity are unknown. Objective: This study aimed to investigate the role of early growth response protein 1 (Egr-1) in the process of As2O3 combined with AZT inhibiting proliferation and inducing apoptosis of human hepatocellular carcinoma HepG2 cells, and explore the possible mechanism. Materials and methods: The expression of Egr-1 was silenced using siRNA, and then HepG2 cells were treated with As2O3 (2 mu M) and AZT (20 mu M). The rates of cell inhibition and apoptosis were determined by the 3-(4,5-Dimetliylthiazol-2-yl)-2,5-diplienyltetrazoliumbromide (MTT) method and flow cytometry, respectively. The mRNA and protein expression of p53, caspase-3, and Egr-1 were detected by real-time quantitative polymerase chain reaction and Western blotting, respectively. Results: The inhibitory rate of As2O3 (2 mu M) combined with AZT (20 mu M) on proliferation of HepG2 cells was significantly higher than that of As2O3 alone. The combination index (CI) values were 0.2 < CI < 0.4, showing strong synergic effect. After silencing Egr-1, the proliferation inhibition and proapoptotie ability of As2O3 combined with AZT on HepG2 cells were decreased, and the CI value was greater than 1, showing antagonistic effect. In addition, the expression of p53 and caspase-3 mRNA/protein was also significantly decreased. Conclusion: The present results show that AZT could increase the sensitization of As2O3 for inhibiting proliferation and promoting apoptosis of HepG2 cells through regulating the expression of Egr-1, which may control the expression of p53 and caspase-3.