重组可溶性TRAIL联合化疗药诱导急性白血病细胞凋亡

首都医科大学学报 ›› 2008, Vol. 29 ›› Issue (3): 364-368.

重组可溶性TRAIL联合化疗药诱导急性白血病细胞凋亡

王宏艳¹, 常瑛²

1. 首都医科大学附属北京友谊医院急诊科;2. 首都医科大学附属北京友谊医院血液科

收稿日期:2007-06-08 修回日期:1900-01-01 出版日期:2008-06-24 发布日期:2008-06-24

rsTRAIL-induced Apoptosis of Acute Leukemic Cells and Its Synergy with Chemotherapeutic Drug

Wang Hongyan¹, Chang Ying²

1. Department of Emergency, Beijing Friendship Hospital, Capital Medical University;2. Department of Hematology, Beijing Friendship Hospital, Capital Medical University

Received:2007-06-08 Revised:1900-01-01 Online:2008-06-24 Published:2008-06-24

摘要/Abstract

摘要： 目的肿瘤坏死相关凋亡诱导配体(TNT-related apoptosis-inducing ligand,TRAIL)作为肿瘤细胞诱导凋亡剂,可单独或与化疗药联合作用诱导多种肿瘤细胞株凋亡.本实验观察重组人可溶性TRAIL是否可有效诱导临床白血病患者的白血病细胞凋亡,并检验化疗药Ara-C联合TRAIL对白血病细胞的杀伤作用.方法将13例原始细胞比例均>60%急性白血病患者的骨髓标本的每份分4组:对照组、TRAIL组、Ara-C组、TRAIL+Ara-C组,进行细胞培养24h后,用AnnexinⅤ及碘化丙啶染色后流式细胞仪观察细胞凋亡率.结果对照组细胞凋亡率为(10.22±7.48)%,TRAIL组为(14.61±11.95)%,Ara-C组为(15.95±11.12)%,TRAIL+Ara-C组为(22.11±15.97)%.将4组标本进行组间方差检验,对照组与TRAIL+Ara-C组比较差异有统计学意义(P=0.015<0.05).在TRAIL组中,13例中有3例(23%)显示对TRAIL诱导的凋亡敏感(若TRAIL组细胞凋亡率高于对照组10%以上,即认为对TRAIL敏感);在TRAIL+Ara-C组中,2例原对TRAIL不敏感的标本及1例对TRAIL敏感标本在TRAIL+Ara-C联合作用下,细胞凋亡率均高于对照组20%以上.结论 1)TRAIL在体外可诱导急性白血病患者的白血病细胞凋亡;2)化疗药Ara-C与TRAIL联合应用可增加白血病细胞的凋亡率,包括先前对TRAIL不敏感的白血病细胞.

Abstract: Objective The TNF-related apoptosis-inducing ligand is currently under evaluation as a possible(co^-)therapeutic in cancer treatment,and it can notably induce the apoptosis of the tumor cells.To study the effect of TRAIL on leukemic cells of the patients,we have investigated the susceptibility of 13 acute leukemic cell samples from acute leukemic patients to TRAIL-induced apoptosis in vitro.Moreover,13 cell samples are coincubated with Ara-C in order to research the synergy between TRAIL and anti-cancer drug.Methods Thirteen leukemic cell samples were from acute leukemic patients who cared in Beijing Friendship Hospital from September 2002 to January 2003.The cell samples contained more than 60% leukemic cells based on morphology criteria.Every cell sample was separated into 4 groups:control group,TRAIL group,Ara-C group,TRAIL+Ara-C group.The cell samples were cultured 24 hours and the apoptotic cells were analyzed by flow cytometry after stained with Annexin Ⅴ and PI.Results Control group:the apoptotic cells were(10.22±7.48)%,TRAIL group:the apoptotic cells were(14.61±11.95)%,Ara-C group:(15.95±11.12)%,TRAIL+Ara-C group:(22.11±15.97)%.There were not significant statistically differences in three groups:control group and TRAIL group(P=0.35),TRAIL group and TRAIL+Ara-C group(P=0.12),Ara-C group and TRAIL+Ara-C group(P=0.19).There was just statistically difference between control group and TRAIL+Ara-C group(P=0.015).Furthermore,3 of 13(15%) cell samples revealed at least 10% TRAIL-susceptibility cells.Coincubated with Ara-C sentitized 2 initially TRAIL-resistant samples to TRAIL-induced apoptosis(>20% specific TRAIL-induced apoptotic cells).Conclusion 1) Only 23% leukemic cell samples are TRAIL sensitive cases;2) Coincubated with TRAIL and Ara-C augmented apoptosis in leukemic cells,including initially TRAIL-resistant samples.

Key words: TNF-related apoptosis-inducing ligand, acute leukemia, cell apoptosis, flow cytometry

中图分类号:

R557

王宏艳;常瑛. 重组可溶性TRAIL联合化疗药诱导急性白血病细胞凋亡[J]. 首都医科大学学报, 2008, 29(3): 364-368.

Wang Hongyan;Chang Ying. rsTRAIL-induced Apoptosis of Acute Leukemic Cells and Its Synergy with Chemotherapeutic Drug[J]. Journal of Capital Medical University, 2008, 29(3): 364-368.

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