Effects of AG1024 on hepatocellular carcinoma cell lines
- VernacularTitle:AG1024对肝癌细胞系增殖与凋亡的影响
- Author:
Dongsheng HUANG
;
Weifeng YAO
;
Junwei LIU
;
Guoliang SHEN
- Publication Type:Journal Article
- Keywords:
Carcinoma,hepatocellular;
Apoptosis;
Receptor IGF type 1;
Enzyme inhibitors
- From:
Chinese Journal of General Surgery
2008;23(9):710-712
- CountryChina
- Language:Chinese
-
Abstract:
Objective Tyrphostin AG1024(3-Bromo-5-t-butyl-4-hydroxybenzylidenemalonitrile) is a specific insulin like growth factor type Ⅰ receptor tyrosine kinase blocker,this study is to investigate the effect of AG1024 on the proliferation and apoptosis of hepatocellular carcinoma cell lines.Methods Treated with AG1024 on vailed concentrations(0～40 μmol/L),human hepatocellular carcinoma cel lines HepG2 and SMMC-7721 were observed for morphological and molecular biology changes,the effect of AG1024 on the cell lines proliferation invasion ability as well as apoptosis was evaluated. Results MTT showed that AG1024 dose-dependently inhibited the proliferation of hepatocellular carcinoma cells,flow cytometry suggested that AG1024 significantly promoted cell lines apoptosis,the cell invasion assay indieated that AG1024 significantly inhibited cell's invasion ability.RT-PCR showed over-expression of IGF-IR in liver cancer cells.and AG1024 dose-dependently increasedtheexpressionofcytochreme C. According totheresultsof Western, blotting,the phosphor-ERK and procaspase-3 were down-regulated while the total ERK remained unchanged. Conclusion AG1024 as a specific IGF-IR blocker blocks the downstream signaling cascade and thus inhibits the proliferation of hepatocellular carcinoma cells and induces cell's apoptosis.
