中国药理学通报2011，Vol.27Issue(8)：1121-1125,5.DOI:10.3969/j.issn.1001-1978.2011.08.021
舒尼替尼对EGFR TKI抵抗的A549细胞株增殖抑制作用及机制研究
Inhibitory effect of sunitinib on EGFR TKI-resistant humannon-small cell lung cancer cell line A549 and its mechanism
摘要
Abstract
Aim To investigate the antiproliferative effects and mechanism of sunitinib on epidermal growth factor receptor tyrosine kinase inhibitors ( ECFR TKI )resistant human non-small cell lung cancer cell line A549 in vitro. Methods A549 cells were exposed to sunitinib. MTT assay was applied to assess the antiproliferative effect. The apoptosis was observed by fluorescence microscope. Cell cycle distributions were analyzed by flow cytometry. The expression of alteration for Bcl-2 was measured by Western blot. Results MTT assay demonstrated sunitinib had remarkable antiproliferative effects and dose-dependent and time-dependent growth inhibition on A549 at the concentration ranged from 0. 4 to 12. 8 μmol · L-1. At 24 .48 ,72 h the ICso of sunitinib on A549 cells was( 7.34 ±0. 76 ).( 5. 54 ± 0. 62 ),( 3. 68 ± 0. 53 )μmol · L-1,respectively. Typical apoptotic morphologic changes,such as karyopyknosis and volume reduction were observed by fluorescence microscope. Cell cycle arrest was significantly observed at the G0/G1 phase. Western blot showed that sunitinib down-regulated the protein level of Bcl-2. With the drug concentration increasing,the expression level for Bcl-2 were gradually suppressed. Coriclusioris Sunitinib can inhibit the growth of EGFR TKI-resistant A549 cells and have the dose-dependent and time-dependent growth inhibition.The mechanism of antitumor may be related to inducing cell cycle arrest and down-regulating the expression of Bcl-2 .关键词
舒尼替尼/肺癌/A549细胞/细胞凋亡/细胞周期/机制/Bcl-2Key words
sunitinib / lung cancer / A549 cells / apoptosis / cell cycle / mechanism / Bcl-2分类
医药卫生引用本文复制引用
潘峰,田静,张旭超,潘跃银..舒尼替尼对EGFR TKI抵抗的A549细胞株增殖抑制作用及机制研究[J].中国药理学通报,2011,27(8):1121-1125,5.基金项目
安徽省科技厅重点资助项目(No 07020304102) （No 07020304102）
