Mechanism of multidrug resistance of human small cell lung cancer cell line H446/VP

<正> Background Small cell lung cancer (SCLC) is the most aggressive form of lung cancer.This study aimed to investigatethe mechanism of human small cell lung cancer cell line resistance to etoposide (VP-16),H446/VP.Methods The cell viability was measured by MTT assay.Immunocytochemistry,reverse transcription-polymerase chainreaction (RT-PCR) and Western blotting methods were used to detect the multidrug resistance gene (MDR1),bcl-2,baxand the topoisomerase Ⅱ (Topo Ⅱ) expressions in H446 and H446/VP cells after treated with or without VP-16.Results The 50% inhibition concentration (IC50) of VP-16 on H446 cells was 49 mg/L,and 836 mg/L was for H446/VPcells.The expressions of MDR1 and bcl-2 were up-regulated,while the amounts of bax and Topo Ⅱ were reduced inH446/VP cells.After treated with 49 mg/L of VP-16,it showed that the drug could significantly inhibit bcl-2 and Topo Ⅱexpressions,and increase bax expression in H446 cells compared with that of H446/VP cells.Conclusions The H446/VP cell was stably resistant to VP-16.The decreased expression of Topo Ⅱ was correlated withthe H446/VP multidrug resistance.The elevated expressions of MDR1,and the altered apoptotic pathways also playedan important role in VP-16 induced multidrug resistance of SCLC.