Cell Biology Division, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, China.
Chin Med J (Engl). 2010 Nov;123(22):3299-303.
Small cell lung cancer (SCLC) is the most aggressive form of lung cancer. This study aimed to investigate the mechanism of human small cell lung cancer cell line resistance to etoposide (VP-16), H446/VP.
The cell viability was measured by MTT assay. Immunocytochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting methods were used to detect the multidrug resistance gene (MDR1), bcl-2, bax and the topoisomerase II (Topo II) expressions in H446 and H446/VP cells after treated with or without VP-16.
The 50% inhibition concentration (IC50) of VP-16 on H446 cells was 49 mg/L, and 836 mg/L was for H446/VP cells. The expressions of MDR1 and bcl-2 were up-regulated, while the amounts of bax and Topo II were reduced in H446/VP cells. After treated with 49 mg/L of VP-16, it showed that the drug could significantly inhibit bcl-2 and Topo II expressions, and increase bax expression in H446 cells compared with that of H446/VP cells.
The H446/VP cell was stably resistant to VP-16. The decreased expression of Topo II was correlated with the H446/VP multidrug resistance. The elevated expressions of MDR1, and the altered apoptotic pathways also played an important role in VP-16 induced multidrug resistance of SCLC.
小细胞肺癌（SCLC）是肺癌中侵袭性最强的一种。本研究旨在探讨人小细胞肺癌细胞系对依托泊苷（VP-16）耐药的机制，即 H446/VP。
采用 MTT 法检测细胞活力。免疫细胞化学、逆转录-聚合酶链反应（RT-PCR）和 Western blot 法检测 H446 和 H446/VP 细胞在未用或用 VP-16 处理后的多药耐药基因（MDR1）、bcl-2、bax 和拓扑异构酶 II（Topo II）的表达。
VP-16 对 H446 细胞的 50%抑制浓度（IC50）为 49mg/L，对 H446/VP 细胞的 IC50 为 836mg/L。H446/VP 细胞中 MDR1 和 bcl-2 的表达上调，而 bax 和 Topo II 的含量减少。用 49mg/L 的 VP-16 处理后，与 H446/VP 细胞相比，H446 细胞中药物能显著抑制 bcl-2 和 Topo II 的表达，增加 bax 的表达。
H446/VP 细胞对 VP-16 稳定耐药。Topo II 的表达降低与 H446/VP 多药耐药有关。MDR1 的高表达和凋亡途径的改变也在 SCLC 中 VP-16 诱导的多药耐药中起重要作用。
