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

中国临床药理学与治疗学 ›› 2014, Vol. 19 ›› Issue (5): 488-492.

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

王猛¹, 黄灿³, 杨翠¹, 夏泉², 许杜娟^1,2

¹安徽医科大学药学院,合肥 230032,安徽;
²安徽医科大学第一附属医院,合肥 230032,安徽;
³安庆市立医院,安庆 246003,安徽

收稿日期:2014-01-23 修回日期:2014-04-25 出版日期:2014-05-26 发布日期:2014-06-05
通讯作者: 许杜娟,女,主任药师,研究生导师,研究方向:肿瘤药理。Tel: 0551-62922422 E-mail: xudujuan6365@aliyun.com
作者简介:王猛,男,硕士,研究方向:肿瘤药理。Tel: 1835195380 E-mail: w594543804@sina.cn
基金资助:
安徽省自然科学基金(11040606M222)

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

WANG Meng¹, HUANG Can³, YANG Cui¹, XIA Quan² , XU Du-juan^1,2

¹School of Pharmacy, Anhui Medical University, Hefei 230032 Anhui,China;
²The First Affiliated Hospital of Anhui Medical University, Hefei 230032, Anhui, China;
³Anqing Municipal Hospital, Anqing 246003, Anhui, China

Received:2014-01-23 Revised:2014-04-25 Online:2014-05-26 Published:2014-06-05

摘要/Abstract

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、 68.14 μg/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、29.44 μg/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。

关键词: 自噬, 凋亡, 肝癌, 3-甲基腺苷, 5-氟尿嘧啶

Abstract: 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 GFP-LC3B 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.

Key words: autophagy, apoptosis, hepatocellular carcinoma, 3-MA, 5-FU

中图分类号:

R965.2

王猛, 黄灿, 杨翠, 夏泉, 许杜娟. 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[J]. 中国临床药理学与治疗学, 2014, 19(5): 488-492.

WANG Meng, HUANG Can, YANG Cui, XIA Quan , XU Du-juan. Adjusting autophagy to augment sensitivity of 5-FU in Bel-7402/FU cells[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(5): 488-492.

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