The study of killing and proapoptotic effects of topoisomerase Ⅰ inhibitor on L1210/ADM cells
- Author:
- No author available
- Journal Title:
- CHINA MEDICINE
- Issue:
- 9
- DOI:
- 10.3760/cma.j.issn.1673-4777.2011.09.010
- Key Word:
- 白血病,淋巴细胞;DNA拓扑异构酶类,Ⅰ型;细胞株;细胞凋亡;Leukemia,lymphocytic;DNA topoisomerases,type Ⅰ;Cell line;Apoptosis
Abstract： Objective To observe the killing and proapoptotic effects of topoisomerase Ⅰ (topotecan) inhibitor on L1210/ADM cells. Methods To analyze the the killing and proapoptotic effects of topoisomerase Ⅰ on L1210/ADM cells with MTT method, Annexin V, DNA ladder electrophoresis and cell morphology analysis. The relation between the killing and proapoptotic effects and Caspase using Caspase-8, inhibitor IETD-fmk and DEVDCHOs was observed. Results In contrast with 0. 05 μ mol/L group, the killing and proapoptotic effects of 0.10 μmol/L topoisomerase inhibitor was statistically different. With 3 groups of Caspase enzyme inhibitor at each time point, survival rate of target topoisomerase group was higher than that of the single-use topoisomerase Ⅰ inhibitor group(P ＜0.05). After treatment with inhibitors of topoisomerase Ⅰ , some target cells died. In Caspase enzyme inhibitor group, some cells died but no apoptotic body formation, dead cells were trypan blue stained. Majority of target cells ever incubated by the topoisomerase Ⅰ inhibitors got dissociated and tufted with each other. Apoptotic bodies formed without trypan blue staining. Target cells electrophoresis showed the characteristic of DNA ladder pattern in the group with Caspase specific inhibitor of the enzyme can block the formation of DNA ladder. Conclusion Topoisomerase Ⅰ inhibitor has significant killing and proapoptotic effects on L1210/ADM cell lines, which can depend on activation of Caspase-8 and Caspase-3.
- [1]林秀英,韩振东,王佳勇,等.阿维A酸诱导皮肤鳞癌细胞凋亡及对caspases蛋白的影响[J].2009,(2).
- [2]高文斌,尹良伟,王怀瑾,等.拓扑替康单药治疗难治性小细胞肺癌的临床评价[J].2003,(5).
- [3]高文斌,尹良伟,王怀瑾,等.TP、HP与NP方案治疗晚期NSCLC的近期疗效[J].2003,(3).
- [4]马海英,崔丽,王杨,等.拓扑替康对小鼠Lewis肺癌的抑制作用[J].2004,(6).
- [5]陈协群,万幼峰,曹云新.金喜素诱导HL-60细胞凋亡依赖caspase活化[J].2001,(6).
- [6]马海英,崔丽,李艳茹,等.拓扑替康对Lewis肺癌细胞和血管内皮细胞结构的影响[J].2004,(4).
- [7]高文斌,韩金娣,杜敏,等.拓扑替康单药治疗21例复发难治性非霍奇金淋巴瘤[J].2006,(5).
- [8]陈协群,万幼峰,白庆咸,等.拓扑异构酶Ⅰ抑制剂对K562细胞的杀伤与诱导凋亡作用[J].2002,(4).
- [9]肖佐环,罗文基,叶礼红,等.半边旗5F对系统性硬皮病患者成纤维细胞半胱氨酸天冬氨酸蛋白酶3活性及其酶原活化的影响[J].2009,(8).
- [10]Thornberry NA,Rosen A,Casciola-Rosen LA,etc.The caspase-3 precursor has a cytosolic and mitochondrial distribution: implications for apoptotic signaling.[J].1998,140(6).
- [11]Danesi R,Del Tacca-M,Di Paolo-A.Preclinical pharmacology and clinical uses of topotecan[J].1999,85(6 Suppl.1).
- [12]M O, Hengartner.The biochemistry of apoptosis.[J].2000,407(6805).
- [13]Bokemeyer C,Kanz L,Kollmannsberger C,etc.Topotecan - A novel topoisomerase I inhibitor: pharmacology and clinical experience.[J].1999,56(1).
- [14]Yokoi A,O'toole K,Kandel JJ,etc.Topotecan is anti-angiogenic in experimental hepatoblastoma.[J].2002,37(6).
- [15]Los M,Schulze-Osthoff K,Stepczynska A,etc.Differential regulation and ATP requirement for caspase-8 and caspase-3 activation during CD95- and anticancer drug-induced apoptosis.[J].1998,188(5).
- [16]韩俊领.一株耐阿霉素小鼠白血病L1210细胞系的建立及耐药机制的研究[J].1995,(2).