摘要
Abstract
Background and objective In the clinical treatment of patients with non-small cell lung cancer (NSCLC), the primary and acquired resistance of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) limits its clinical application, this need to explore new strategy or method to overcome this problem. Recently, some literatures have indicated that the antitumor role of heat shock protein 90 (HSP90) inhibitors by a variety of pathways may provide new strategy for resolving this problem. In this study, we examined the effect of 17-DMAG on NSCLC cell lines A549 and H1975 which were primary and acquired resistant to EGFR-TKI respectively, the purpose was to explore its inlfuence on cell prolifera-tion, apoptosis and the expression of EGFR in vitro as well as possible mechanism. Methods Atfer A549 and H1975 cell lines were treated with different concentrations of 17-DMAG respectively, the inhibitory rate of cell proliferation was measured by MTT assay in 24 h, 48 h and 72 h. We investigated the effect of 17-DMAG on the cell apoptosis with lfow cytometry and the ex-pression of HSP90 and EGFR with Western blot atfer treated with 17-DMAG for 48 h. Results Atfer treated with 17-DMAG, the inhibitory rate of different concentrations and time groups was signiifcant (P<0.01), and the effect was in time-and dose-dependent manner;the apoptosis rate of both two cell lines in all treated groups were signiifcantly higher than control group (P<0.01), and the effect was in dose-dependent manner. By Western blot analysis, there was no signiifcant difference between all treated groups and control group for the expression of both HSP90 and EGFR protein in A549 cell line and HSP90 protein in H1975 cell line atfer exposed to 17-DMAG for 48 h (P>0.05), while the difference was signiifcant for the expression of EGFR protein in H1975 cell line (P<0.01). Conclusion 17-DMAG inhibited the proliferation of NSCLC cell lines A549 and H1975 and also induced apoptosis of both cell lines. It down-regulated the expression of mutant EGFR protein while this phe-nomenon was not observed in EGFR-wild type cell line. hTis suggested that the mechanism maybe different between A549 and H1975 cell lines with different genetic backgroud. Our study provided new strategy for treatment with NSCLC being resistant to EGFR-TKI.关键词
肺肿瘤/热休克蛋白90抑制剂/表皮生长因子受体酪氨酸激酶抑制剂/增殖/凋亡Key words
Lung neoplasms/HSP90 inhibitors/EGFR-TKI/Proliferation/Apoptosis
