多西他赛与吉非替尼序贯应用对人肺腺癌细胞H1975存活及凋亡通路的研究

BACKGROUND AND OBJECTIVE: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib show promising therapeutic effects in patients with advanced non-small cell lung cancer (NSCLC). However, despite an initial response to EGFR-TKIs treatment among responsive patients, most inevitably acquire resistance after a progression-free period of about 10 months. The percentage of T790M in TKI acquired-resistant patients in most studies is around 50%. The aim of this study is to assess the effects of the sequential administration of docetaxel and gefitinib on cell proliferation and apoptosis of lung adenocarcinoma cell H1975. METHODS: An MTT assay was used to measure cell proliferation. The potency of the sequential administration of docetaxel and gefitinib were determined by isobolograms and combination index (CI). Cell apoptosis and cycle distribution were determined by flow cytometry. The Hoechst 33258 method was used to observe the apoptotic morphology. Chemical colorimetric luminescence was used to measure the caspase activity. RESULTS: The isobolograms and CI showed that the sequential administration of docetaxel following gefitinib remarkably inhibits cell proliferation and cell apoptosis compared with other sequential administration models. The cycle distribution results indicate that sequential docetaxel administration following gefitinib blocked the cells in the G(2)/M phase but not in the G(0)/G(1). The activation of the Caspase-8/Caspase-3 cascade is mainly involved in the apoptotic pathway of lung adenocarcinoma cell H1975 in all sequential administration models. CONCLUSION: The docetaxel administration following gefitinib might be a new stratagy for lung cancer with T790M mutation after having EGFR-TKIs resistance