Epidermal growth factor receptor inhibitor AG1478 affects HepG2 cell proliferation, cell cycle, apoptosis and c-Myc protein expression in a dose-dependent manner

Wenqi Wang,Mingxian Yan,Changhong Liu,Yiguo Wang,Yaru Wang,Liyun Wang,Jinhua Fan

doi:10.1080/13102818.2018.1460620

Abstract

ABSTRACTThe aim of this study was to observe the effect of AG1478, an inhibitor of the epidermal growth factor receptor, on cell proliferation, cell cycle and apoptosis of human hepatoma HepG2 cells. Cell counting kit-8 assay was employed to examine the survival rates of cultured HepG2 cells after treatments with different concentrations of AG1478 for 24 h. Flow cytometry was performed to determine the effect of AG1478 on cell cycle and apoptosis. Immunohistochemistry was used to measure the expression of c-Myc protein. The survival rates of human hepatoma HepG2 cells after treatments with 5, 10, 20 and 40 μmol/L of AG1478 for 24 h were 76.0%, 59.6%, 51.2% and 42.1%, respectively. The apoptotic rates after treatments with 5, 10, 20 and 40 μmol/L of AG1478 were (12.88 ± 1.91)%, (23.16 ± 2.67)%, (35.36 ± 1.95)% and (47.16 ± 3.78)%, respectively. HepG2 cells were mainly arrested in the G0/G1 phase after treatment with 10, 20 and 40 μmol/L of AG1478. The c-Myc protein was highly expressed in HepG2 cells, whereas treatment with 20 μmol/L AG1478 substantially inhibited its expression. Overall, AG1478 inhibited the proliferation of human hepatoma cells in vitro, arrested the cells in G0/G1 phase, induced apoptosis and reduced the expression of c-Myc protein. These results also indicated that AG1478 blocked the proliferation and induced apoptosis of hepatoma cells in a dose-dependent manner.

Highlights

Primary liver carcinoma is one of the mostly detectable cancers, with a total of 630,000 new liver cancer cases and 600,000 deaths all over the world every year
The aim of this study was to observe the effect of AG1478, an inhibitor of the epidermal growth factor receptor, on cell proliferation, cell cycle and apoptosis of human hepatoma HepG2 cells
AG1478 inhibited the proliferation of human hepatoma cells in vitro, arrested the cells in G0/G1 phase, induced apoptosis and reduced the expression of c-Myc protein. These results indicated that AG1478 blocked the proliferation and induced apoptosis of hepatoma cells in a dose-dependent manner

Summary

Introduction

Primary liver carcinoma (hepatocellular carcinoma) is one of the mostly detectable cancers, with a total of 630,000 new liver cancer cases and 600,000 deaths all over the world every year. Phosphorylated tyrosine kinase mediates the transduction of cytoplasmic signals into the nucleus through multiple pathways, such as Ras/Raf/mitogenactivated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) [7,8,9]. This process changes cell cycle-related genes, induces cancer cell proliferation and suppresses apoptosis [10,11]. Jiang et al [15] reported that EGFR was highly expressed in human hepatoma tissues, and EGF might induce cancer cell proliferation through MAPK/ extracellular signal-regulated kinase (ERK) pathway. AG1478, an EGFR-specific inhibitor, can suppress this process effectively, suggesting that EGFR can be an ideal target of anti-cancer drugs

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