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姜黄素联合环磷酰胺对人耐药淋巴瘤细胞株HT/CTX生长的抗增殖作用及其与FA/BRCA通路的关系

[Antiproliferative effect of curcumin combined with cyclophosmide on the growth of human lymphoma cell line HT/CTX with drug resistance and its relation with FA/BRCA pathway].

作者信息

Xiao Hui, Zhang Ke-Jian

机构信息

Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China.

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2008 Aug;16(4):804-8.

Abstract

The aim of this study was to investigate the antiproliferative effect of curcumin combined with cyclophosmide on the growth of human lymphoma cell line HT/CTX with drug resistance and its relation with FA/BRCA pathway. The inhibitory effects of the drugs on the growth of HT/CTX cells were determined by MTT assay. Cell cycle phase and apoptosis were analyzed by flow cytometry. The expression of FANCD2 protein in FA/BRCA pathway was determined by Western blot. The results indicated that the combination of curcumin with CTX had an additional synergistic inhibitory effects on the proliferation and cell cycle distribution of HT/CTX cells. The curcumin could enhance toxicity of CTX on HT/CTX cells through inhibition of FA/BRCA pathway which was realized by suppression of FANCD2 monoubiquitination. The curcumin combined with CTX could increase apoptosis inducing effect on HT/CTX cells, while the curcumin or CTX alone did not showed this effect, and without inhibition of FA/BRCA pahtway. It is concluded that combination of curcumin and CTX produces synergistic effects and reverses multiple drug resistance of HT/CTX cells effectively. The prevention of cells from entering the next cell cycle and down regulation of FANCD2 protein monoubiquitination may be involved in the mechanism.

摘要

本研究旨在探讨姜黄素联合环磷酰胺对人淋巴瘤耐药细胞株HT/CTX生长的抗增殖作用及其与FA/BRCA通路的关系。采用MTT法检测药物对HT/CTX细胞生长的抑制作用。通过流式细胞术分析细胞周期阶段和凋亡情况。采用蛋白质免疫印迹法检测FA/BRCA通路中FANCD2蛋白的表达。结果表明,姜黄素与环磷酰胺联合使用对HT/CTX细胞的增殖和细胞周期分布具有额外的协同抑制作用。姜黄素可通过抑制FA/BRCA通路增强环磷酰胺对HT/CTX细胞的毒性,这是通过抑制FANCD2单泛素化实现的。姜黄素联合环磷酰胺可增强对HT/CTX细胞的凋亡诱导作用,而单独使用姜黄素或环磷酰胺则无此作用,且不抑制FA/BRCA通路。结论是姜黄素与环磷酰胺联合使用可产生协同作用,并有效逆转HT/CTX细胞的多药耐药性。其机制可能与阻止细胞进入下一个细胞周期以及下调FANCD2蛋白单泛素化有关。

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