摘要
目的:探讨蛋白酪氨酸磷酸酶(PTEN)蛋白表达对酪氨酸激酶抑制剂(TKI)耐药性的影响。方法:采用H-157和H-1355肺癌细胞体外培养,两种细胞均分为空白对照组和酪氨酸激酶抑制剂处理组。应用细胞生长曲线评价酪氨酸激酶抑制剂对细胞的抑制作用;应用流式细胞术检测细胞凋亡和周期;应用蛋白质印迹法测定细胞表皮生长因子受体(EGFR)和PTEN蛋白表达并评价PTEN表达对TKI疗效的影响。结果:H-157和H-1355两种肺癌细胞均呈现EGFR高表达,但H-1355细胞PTEN蛋白呈现高表达,而H-157细胞PTEN表达很低。应用TKI处理后,H-157细胞生长未见明显抑制,t=1.13,P>0.05;而H-1355细胞生长曲线下移明显,t=7.95,P<0.05。流式细胞仪检测显示,H-1355细胞TKI处理后导致(11.74±1.93)%的凋亡率(q=14.26,P<0.01)以及(83.74±3.93)%的G1期阻滞(q=9.54,P<0.01),而H-157细胞凋亡和G1期阻滞的百分率分别为(3.18±0.61)%(q=2.11,P>0.05)和(63.65±4.61)%(q=1.75,P>0.05)。结论:PTEN基因是TKI对肿瘤细胞抑制作用的重要调节因子,PTEN低表达导致肿瘤细胞对TKI原发耐药。
OBJECTIVE： To investigate the resistance to epidermal growth factor receptor tyrosine kinase inhibitors mediated by the expression of the PTEN tumor-suppressor protein. METHODS： H-157 and H-1355 cell lines were cultivated in vitro. There were control group and TKI group in all experiments. The EGFR and PTEN expressions were determined by Western blotting. The cell growth curve was used for cell survival experiment. The cell cycle distribution and apoptosis were analyzed by flow cytometry. RESULTS： H-157 and H-1355 of lung cancer cells showed a high expression of EGFR, but H-1355 cells showed a high expression of PTEN protein, and the PTEN expression of H-157 cells was very low. Being treated with TKI, the growth of H-1355 was inhibited significanly（t =7. 95,P〈0. 05）, but that of H-157 not（t=1.13,P〉0. 05）. The TKI led（11. 74±1. 93）% apoptosis of H-1355 cells（q= 14. 26, P〈0. 01） and（3. 18±0. 61）% of H-157 cells（q= 2. 11,P〉 0. 05）. Compared with the H-157 cells related to little cell cycle arrest（63.65±4. 61） % （q= 1.75, P〉0. 05）, more G1 cell cycle arrest（83. 74±3. 93）% walked on H-1355 cells（q= 9. 54, P〈0.01）. CONCLUSIONS： PTEN gene is an important regulator on TKI inhibition of tumor cells. The PTEN low expression in- duced drug-resistance to TKI in tumor cells.
出处
《中华肿瘤防治杂志》
CAS
2009年第14期1055-1058,共4页
Chinese Journal of Cancer Prevention and Treatment
关键词
肺肿瘤/病理学
基因
肿瘤抑制
细胞周期
细胞凋亡
lung neoplasms/pathology
genes, tumor suppressor
cell cycle arrest apoptosis
