调节自噬提高人肝癌Bel-7402/FU细胞株对5-氟尿嘧啶的敏感性  

Adjusting autophagy to augment sensitivity of 5-FU in Bel-7402/FU cells

作　　者：王猛[1] 黄灿[2] 杨翠[1] 夏泉[3] 许杜娟[1,3] 

机构地区：[1]安徽医科大学药学院 [2]安庆市立医院 [3]安徽医科大学第一附属医院

出　　处：《中国临床药理学与治疗学》2014年第5期488-492,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：安徽省自然科学基金(11040606M222)

摘　　要：目的:探讨细胞自噬对肝癌Bel-7402/FU细胞5-氟尿嘧啶敏感性的影响。方法:选取Bel-7402、Bel-7402/FU细胞株,分为对照组、5-氟尿嘧啶组、自噬抑制剂3-甲基腺苷组以及5-氟尿嘧啶+3-甲基腺苷组,MTT法了解抑制细胞自噬对肝癌5-氟尿嘧啶IC50值的影响;流式细胞术检测抑制细胞自噬对细胞凋亡的影响;GFP-LC3质粒转染观察细胞浆中GFP-LC3分布情况。结果:Bel-7402细胞株与Bel-7402/FU细胞株5-氟尿嘧啶IC50值分别为4.66、68.14μg/mL,凋亡率分别为13.80%、1.09%。3-甲基腺苷联合5-氟尿嘧啶作用后Bel-7402细胞株与Bel-7402/FU细胞株的氟尿嘧啶IC50值分别为4.31、29.44μg/mL,凋亡率分别为13.82%、6.86%。在3-甲基腺苷作用下,Bel-7402/5-FU细胞株5-氟尿嘧啶诱导的点状样GFP-LC3的细胞数量减少。结论:抑制细胞自噬可降低Bel-7402/FU对5-氟尿嘧啶IC50值,诱导细胞凋亡,从而有效地逆转Bel-7402/FU对5-氟尿嘧啶耐药。AIM： To explore the effects of autophagy in the sensitivity of Hepatocellular carcinoma cells line Bel-7402/FU to 5-FU. METHODS： Hepatocellular carcinoma cells lines Bel-7402 and Bel-7402/FU were treated with 5-FU or 3-MA, or pretreated with 3-MA followed by 5-FU. MTT method test was used to determine the proliferative inhibition rate. Flow cytometry was used to examine cell apoptosis. The GFPLC3B morphological changes were observed by fluorescent microscope. RESULTS： The IC50 values of 5-FU in Bel-7402 and Bel-7402/FU cells were 4.66 μg /mL and 68.14 μg /mL, respectively. The apoptosis rates of the Bel-7402 and Bel-7402/FU were 13.80% and 1. 09%, respectively. When 5-FU was used combined with 3- MA, the IC50 values of 5-FU in Bel-7402 and Bel-7402/FU cells were 4.31 μg /mL and 29.44 μg /mL. The apoptosis rates of Bel-7402 and Bel-7402/FU were 13.82% and 6.86%, respectively. 3-MA decreased 5-FU-induced punctuate spot formation in Bel-7402/FU. CONCLUSION： Autophagy is connected with 5-FU-resistance and inhibition of autophagy can reverse 5-FU-resistance in Bel-7402 /FU.

关 键 词：自噬 凋亡 肝癌 3-甲基腺苷 5-氟尿嘧啶 

分 类 号：R965.2[医药卫生—药理学]