Mechanism of EGFR inhibitor AG1478 combined with oxaliplatin in inhibiting PI3K/AKT pathway and promoting autophagy in HI 975 cells / 中国药理学通报

Aim To explore the effect of oxaliplatin combined with epidermal growth factor receptor tyrosine kinase inhibitor AG1478 on autophagy in non-small cell lung cancer H1975 cells. Methods H1975 cells were cultured in vitro using gradient concentrations of AG1478 (0, 5, 10, 15, 20, 25, 30, 35, 40 jjimol • IT

EGFR inhibitor AG1478 enhances oxaliplatin induced apoptosis in HCT116 cells / 中国药理学通报

Aim To investigate the effect of tyrosine kinase inhibitor AG1478 combined with oxaliplatin (OXA) on apoptosis of colorectal cancer HCT116 cells. Methods MTT assay was used to measure the effect of AG1478 combined with OXA on proliferation of HCT116 cells. RT-qPCR was used to detect the mRNA expression levels of p53, caspase-3, Bcl-2 and Bax. Western blot was used to detect the proteins expression of p53, caspase-3, cleaved-caspase 3, Bcl-2, Bax, p62, LC3 and IL-6. Results Both OXA and AG1478 inhibited the proliferation of HCT116 (P < 0. 01). IC

Effect of epidermal growth factor receptor inhibitor AG1478 induces cell death in HeLa cells / 实用医学杂志

Objective To investigate the biological features of epidermal growth factor receptor inhibitor AG1478 on cervical carcinoma cell. Methods The proliferation of HeLa cells under AG1478 stimulation was determined by CCK8 assay. The expression of EGFR downstream signaling protein and apoptotic relative protein were examined by Western blot and transcription of apotosis?related genes were measured by RT?qPCR in AG 1478 treated HeLa cells. Nuclear transport of phosphorylated ERK were measured through ICC assay. TUNEL assay was used to determine early stage of apoptosis. Results CCK8 assay showed that AG1478 inhibit the proliferation of HeLa cells and also block phosphorylated level of EGFR ,ERK and AKT. Furthermore ,nuclear transport of phosphorylated ERK upon EGF stimulation were blocked and pro?apoptotic proteins were up?regluated with activat ed cleaved Caspases. Conclusion AG1478 inhibited the proliferation and induced apoptosis in HeLa cells and it could be a potential therapeutic drug for cervical carcinoma.

EGFR Inhibitor Enhances Cisplatin Sensitivity of Human Glioma Cells / 华中科技大学学报（医学）（英德文版）

Epidermal growth factor receptor (EGFR) is found to express at high levels in a variety of　solid tumors including gliomas.This study was to examine the effect of an EGFR-tyrosine kinase inhibitor (AG1478) alone or in combination with cisplatin (CDDP) on the growth of glioma cells (U87).U87 glioma cells were treated with AG1478 (10 μmol/L) or CDDP (25 μmol/L) as a single agent or in　combination for 24 or 48 h.The expression of EGFR and the components in its downstream signaling　pathway [extracellular signal-regulated kinase (ERK),protein kinase B (AKT)] in U87 glioma cells was　detected by Western blotting.Cell growth,cell cycle distribution and cell apoptosis were determined by　MTT method and flow cytometry,respectively.The results showed that CDDP could induce the activation of EGFR and the components in its downstream signaling pathways in a concentration-dependent　manner.The combined treatment of AG 1478 with CDDP could inhibit the proliferation of U87 glioma　cells,arrest the cell cycle and promote cell apoptosis.In the EGFR signaling pathway,AG1478 decreased the phosphorylation of ERK,AKT and EGFR in U87 glioma cells.It was concluded that the　combined treatment of AG1478 and CDDP may exert synergistic inhibitory effects on the growth of　glioma cells by suppressing the activities of EGFR,AKT and ERK.