Reversal of chemoresistance and enhancement of apoptosis by statins through down-regulation of the NF-κB pathway
Reversal of chemoresistance and enhancement of apoptosis by statins through down-regulation of the NF-κB pathway
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DOI：
10.1016/j.bcp.2007.10.010
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发表时间：
2008-02-15
影响因子：
5.8
通讯作者：
Aggarwal, Bharat B.
中科院分区：
文献类型：
--
作者：
Ahn, Kwang Seok;Sethi, Gautam;Aggarwal, Bharat B.
我们最近发现辛伐他汀可以调节核因子-kappaB(NF-kappa B)的激活途径，但其他他汀类药物是否具有与辛伐他汀类似的作用尚不清楚。因此，我们评价了六种不同的他汀类药物对肿瘤坏死因子诱导的人髓系白血病细胞中核因子-kappaB活化的影响。然后，我们确定他汀类药物和标准化疗药物的组合是否可以克服化疗耐药并增强细胞凋亡。在评估的六种他汀类药物中，只有天然的他汀类药物(辛伐他汀、美伐他汀、洛伐他汀和普伐他汀)，而不是合成的他汀类药物(氟伐他汀和阿托伐他汀)能抑制肿瘤坏死因子诱导的核因子-kappaB的激活。辛伐他汀抑制多柔比星、紫杉醇和5-氟尿嘧啶诱导的核因子-kappaB的活化，并增强其诱导的细胞凋亡。这些结果表明，不同的他汀类药物的作用不同，它们可能有助于克服化疗耐药。(C)2007 Elsevier Inc.保留所有权利。
We recently found that simvastatin can modulate the nuclear factor-kappa B (NF-kappa B) activation pathway, but whether other statins have similar effects to those of simvastatin is unknown. Therefore, we evaluated the effect six different statins on TNF-induced NF-kappa B activation in human myeloid leukemia cells. We then determined whether the combination of statins and standard chemotherapeutic agents could overcome chemoresistance and augment apoptosis. Of the six statins evaluated, only the natural statins (simvastatin, mevastatin, lovastatin, and pravastatin), not the synthetic statins (fluvastatin and atorvastatin), inhibited TNF-induced NF-kappa B activation. Simvastatin suppressed the NF-kappa B activation and potentiated the apoptosis induced by doxorubicin, paclitaxel, and 5-fluorouracil. These results suggest that different statins behave differently from one another and that they may be useful in overcoming chemoresistance. (c) 2007 Elsevier Inc. All rights reserved.