The mechanism of rheum emodin reversed resistance of EGFR-TKI in NSCLC

OUYANG Xuenong; FANG Wenzheng; WU Dansen; LIN Shaoqin; Chen Juan; YU Zongyang

Abstract：Objective To investigate the mechanism of rheum emodin reversed resistance of epidermal growth factor receptor tyrosine kinase inhibitors(EGFR?TKI) in non?small cell lung cancer(NSCLC). Methods NSCLC cell lines resistant to EGFR?TKI ( HCC827/GR) was built by continuous induction method. MTS method was used to detect the ability of cell proliferation by treating HCC827 and HCC827/GR cells with rheum emodin( 30μmol/L) , gefitinib( 1μmol/L) and rheum emodin( 30μmol/L) combined with gefitinib(1μmol/L). The expressions of p?EGFR, p?AKT, p?ERK1/2 and p?MET in HCC827 and HCC827/GR cells were detected by Western blotting method. Results The proliferation ability of HCC827/GR cell was not decreased by treating gefitinib or rheum emodin monotherapy, but remarkably decreased by treating the combination of gefitinib and rheum emodin, with statistical difference( P<0?05) . The expressions of p?EGFR and p?ERK were strong and p-AKT expression was weak in HCC827 and HCC827/GR. p?MET expression was significantly increased in HCC827/GR compared with HCC827. After treated with 1μmol/L gefitinib, the expressions of p?EGFR and p?ERK were down?regulated in HCC827, and the expression of p?EGFR was significantly descended in HCC827/GR cell. 30μmol/L rheum emodin could obviously reduce the expression of p?MET in HCC827/GR. Otherwise, after treated with rheum emodin and gefitinib, the expressions of p?EGFR, p?ERK1/2 and p?MET were markedly inhibited. Conclusion Rheum emodin may reverse the resistance of EGFR?TKI in NSCLC, probably by inhibiting the activation of c?Met.