eIF5A1对非小细胞肺癌细胞系化疗药物敏感性的影响  

Effect of e IF5A1 gene on chemosensitivity of human NSCLC cell lines

作　　者：李彦琦[1] 李嵚[2] 何琳[2] 惠林萍[2] 许崇安[1] 

机构地区：[1]中国医科大学附属第四医院肿瘤内科,辽宁沈阳110032 [2]中国医科大学附属第四医院中心实验室,辽宁沈阳110032

出　　处：《现代肿瘤医学》2015年第5期608-613,共6页Journal of Modern Oncology

摘　　要：目的:探讨e IF5A1对非小细胞肺癌(non-small cell lung cancer,NSCLC)细胞系化疗药物敏感性的影响及可能的机制。方法:应用RT-PCR法检测不同NSCLC细胞系e IF5A1 mRNA表达水平。MTT法检测其对吉西他滨的敏感性,并分析二者的关系。构建真核表达载体p EGFP-C1-e IF5A1并通过脂质体介导法转染肺腺癌LTEP-a-2细胞。荧光显微镜、RT-PCR和Western blot方法评估转染效率。MTT法检测转染后细胞化疗药物敏感性变化。流式细胞仪检测转染后细胞周期及凋亡变化。结果:肺鳞癌细胞系e IF5A1mRNA表达水平及对吉西他滨的敏感性均显著高于肺腺癌细胞系(P<0.001)。p EGFP-C1-e IF5A1转染e IF5A1表达水平最低的LTEP-a-2细胞后e IF5A1 mRNA及蛋白表达水平显著升高(P<0.001)。与对照组细胞比较,e IF5A1转染组细胞对吉西他滨、顺铂、紫杉醇、多西紫杉醇的敏感性显著增加(P<0.001)。S期和G2/M期细胞比例显著增加(P<0.001)。在化疗药物作用下,细胞凋亡率显著增加(P<0.001)。结论:在非小细胞肺癌中上调e IF5A1的表达可能增加细胞对化疗药物的敏感性,其机制可能与e IF5A1高表达增强化疗药物的促凋亡作用及影响细胞周期分布有关。Objective：To investigate the effect of eIF5A1 gene on chemosensitivity of human NSCLC cell lines and the possible mechanism. Methods：Expression levels of eIF5A1 mRNA in different NSCLC cell lines were measured by RT - PCR . The sensitivities to gemcitabine for cells were detected by MTT assay. The correlation between the a-bove two was analysized. The eukaryotic expression plasmid pEGFP - C1 - eIF5A1 was constructed and transfected in-to the LTEP - a - 2 cells by liposome transfection reagent. The transfection was proved effective by the fluorescence microscopy,RT - PCR and Western blot. MTT assay was used to investigate the effects of eIF5A1 overexpression on the drug sensitivities of LTEP - a - 2 cells. The change of apoptosis rate and cell cycle were detected by flow cytome-try（FCM）. Results：Lung squamous cell lines had higher eIF5A1 expression levels and sensitvities to gemcitabine than adencarcinoma cell lines（P 〈 0. 001）. eIF5A1 mRNA and protein expression levels of LTEP - a - 2 cell line with the lowest eIF5A1 expression level were significantly increased after transfection with pEGFP - C1 - eIF5A1（P〈 0. 001）. Compaired with the empty vector group or un - transfected group,the sestivities to cisplatin,gemcitabine, paclitaxel,docetaxel were significantly increased for eIF5A1 gene transfected group（P 〈 0. 001）,inforced eIF5A1 ex-pression increased the cell cycle arrest in S and G2 ∕ M phase（P 〈 0. 001）. With the treatment of chemotherapeutic a-gents,the cell apoptosis also significantly increased in the eIF5A1 gene transfected group（P 〈 0. 001）. Conclusion：Overexpression of eIF5A1 in non - small cell lung cancer may increase the sensitivity of cells to chemotherapeutic a-gents. eIF5A1 may influence chemosensitivity of non - small cell lung cancer through promoting apoptosis - accelera-ting effects of chemotherapeutic agents and changing the cell cycle.

关 键 词：非小细胞肺癌 eIF5A1 化疗药物敏感性 

分 类 号：R734.2[医药卫生—肿瘤]