Effects of triptolide from Tripterygium wilfordii on ERα and p53 expression in two human breast cancer cell lines
Effects of triptolide from Tripterygium wilfordii on ERα and p53 expression in two human breast cancer cell lines
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DOI：
10.1016/j.phymed.2009.03.021
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发表时间：
2009-11-01
期刊：
影响因子：
7.9
通讯作者：
Zhang, Luyong
中科院分区：
文献类型：
--
作者：
Liu, Jing;Jiang, Zhenzhou;Zhang, Luyong
本研究的目的是发现雷公藤甲素对雌激素敏感的MCF-7与雌激素不敏感的MDA-MB-231人乳腺癌细胞可能的差异细胞毒性。考虑到MCF-7细胞表达功能性雌激素受体α，（ER α）和野生型p53，而ER α阴性的MDA-MB-231细胞表达突变型p53，检测了雷公藤内酯醇对MCF-7和MDA-MB-231细胞的抗增殖作用，研究了雷公藤内酯醇引起的凋亡作用和细胞周期阻滞，同时观察了ER α和p53的表达。结果表明，雷公藤内酯醇对两种细胞株均有抑制增殖作用。但其对MCF-7细胞增殖抑制作用的IC_（50）值约为对MDA-MB-231细胞增殖抑制作用的十分之一，表明其对MCF-7细胞的抑制作用更强。仅用40 nM雷公藤内酯醇处理的MCF-7细胞中可观察到染色质浓缩或核碎裂，而在MDA-MB-231细胞中，直到浓度达到400 nM才能观察到染色质浓缩或核碎裂。雷公藤内酯醇诱导MDA-MB-231细胞出现明显的S期阻滞，并伴随沿着亚G 0/G1峰的出现，而MCF-7细胞仅出现轻微的S期阻滞。检测了p53在两种乳腺癌细胞中的作用，结果显示突变型p53在MDA-MB-231细胞中被抑制，而野生型p53在MCF-7细胞中被增加。雷公藤内酯醇可下调MCF-7细胞ER α的表达。结果表明，雷公藤内酯醇对ER α阳性的MCF-7细胞比ER α阴性的MDA-MB-231细胞更敏感，并且敏感性与ER α和p53状态显著相关。(C)2009年Elsevier GmbH。All rights reserved.
The aim of the study was to discover possible differential cytotoxicity of triptolide towards estrogen-sensitive MCF-7 versus estrogen-insensitive MDA-MB-231 human breast cancer cells. Considering that MCF-7 cells express functional Estrogen receptor alpha (ER alpha) and wild-type p53, whereas MDA-MB-231 cells which are ER alpha-negative express mutant p53, the anti-proliferation effect of triptolide on MCF-7 and MDA-MB-231 cells were examined, the apoptotic effect and cell cycle arrest caused by triptolide were investigated, ER alpha and p53 expression were also observed in this paper. The results showed that the anti-proliferation effects were induced by triptolide in both cell lines. But the value of IC50 in MCF-7 cells for its anti-proliferation effect was about one tenth of that in MDA-MB-231 cells, which indicated that the effect is more potent in MCF-7 cells. Condensed chromatin or fragmented nuclei could be found in MCF-7 cells treated with only 40 nM triptolide but in MDA-MB-231 cells they couldn't be observed until the concentration reached to 400 nM. Triptolide induced significant S cell cycle arrest along with the presence of sub-G0/G1 peak in MDA-MB-231 cells, whereas there was only slightly S cell cycle arrest on cell cycle distribution in MCF-7 cells. The role of p53 in two breast cancer cells was examined, the results showed that the mutant p53 in.MDA-MB-231 cells was suppressed and the wild-type p53 in MCF-7 was increased. Moreover, triptolide could down regulate the expression of ER alpha in MCF-7 cells. The results showed that triptolide is much more sensitive to ER alpha-positive MCF-7 cells than to ER alpha-negative MDA-MB-231 cells, and the sensitivity is significantly associated with the ER alpha and p53 status. (C) 2009 Elsevier GmbH. All rights reserved.