Realgar-induced apoptosis and differentiation in all-trans retinoic acid (ATRA)-sensitive NB4 and ATRA-resistant MR2 cells.

Realgar-induced apoptosis and differentiation in all-trans retinoic acid (ATRA)-sensitive NB4 and ATRA-resistant MR2 cells.
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雄黄诱导全反式视黄酸(ATRA)敏感的 NB4 和 ATRA 耐药的 MR2 细胞凋亡和分化

DOI:
10.3892/ijo.2011.1276
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发表时间:
2012-04
影响因子:
5.2
通讯作者:
Li X
Li X
中科院分区:
医学2区
文献类型:
--
作者:
Chen S;Fang Y;Ma L;Liu S;Li X

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雄黄自古以来就被用于西药和中药中,近年来雄黄具有良好的抗癌活性,特别是对急性早幼粒细胞白血病(APL)的治疗受到了广泛关注。然而,雄黄治疗APL的治疗作用仍有待充分阐明。对经雄黄处理的PML-RARα+ APL患者的细胞毒性、增殖、凋亡和分化进行了全面研究,包括全反式维甲酸(ATRA)敏感的NB4和耐ATRA的MR2细胞。为了分析凋亡和分化的关键调控因子,我们在NB4细胞中进行了基因表达谱分析。雄黄对两种细胞系均有诱导细胞凋亡和分化的作用,且这些作用是同时发生的。基因表达谱表明,雄黄处理影响的基因参与了信号转导、翻译、转录、代谢和免疫应答的调节。雄黄具有较低的毒性,是一种很有前途的治疗APL的替代试剂。我们的数据有助于理解雄黄在APL临床治疗中的治疗作用的潜在机制。
Realgar has been used in Western medicine and Chinese traditional medicine since ancient times, and its promising anticancer activity has attracted much attention in recent years, especially for acute promyelocytic leukemia (APL). However, the therapeutic action of realgar treatment for APL remains to be fully elucidated. Cellular cytotoxicity, proliferation, apoptosis and differentiation were comprehensively investigated in realgar-treated cell lines derived from PML-RARα+ APL patient, including the all-trans retinoic acid (ATRA)-sensitive NB4 and ATRA-resistant MR2 cell lines. For analysis of key regulators of apoptosis and differentiation, gene expression profiles were performed in NB4 cells. Realgar was found to induce apoptosis and differentiation in both cell lines, and these effects were exerted simultaneously. Gene expression profiles indicated that genes influenced by realgar treatment were involved in the modulation of signal transduction, translation, transcription, metabolism and the immune response. Given its low toxicity, realgar is a promising alternative reagent for the therapy of APL. Our data contribute to an understanding of the underlying mechanism responsible for the therapeutic effects of realgar in the clinical treatment of APL.
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