EGF Reverses Multi-drug Resistance via the p-ERK Pathway in HepG2/ADM and SMMC7721/ADM Hepatocellular Carcinoma Models


Aim: To investigate signaling pathways for reversal of EGF-mediated multi-drug resistance (MDR) inhepatocellular carcinoma (HCC) models. Materials and
Methods: HCC MDR cell strain HepG2/adriamycin(ADM) and SMMC7721/ADM models were established using a method of exposure to medium with ADMbetween low and high concentration with gradually increasing concentration. Drug sensitivity and reversalof multi-drug resistance by EGF were determined and the cell cycle distribution and apoptosis were analyzedby flow cytometry. Phosphorylation of ERK1, ERK2, ERK5 and expression of Bim were detected by Westernblotting.
Results: The results showed that HepG2/ADM and SMMC7721/ADM cells were resistant not only toADM, but also to multiple anticancer drugs. When used alone, EGF had no anti-tumor activity in HepG2/ADMand SMMC7721/ADM cells in vitro, while it increased the cytotoxicity of ADM. EGF induced cell apoptosis andG0/G1 phase cell cycle arrest in HepG2/ADM And SMMC7721/ADM cells, while enhancing activity of p-ERKsand up-regulated expression of BimEL.
Conclusions: EGF might enhance the chemosensitivity of HepG2/ADMand SMMC7721/ADM cells via up-regulating p-ERKs and BimEL protein.