Chloroquine inhibits cell growth and induces cell death in A549 lung cancer cells
Chloroquine inhibits cell growth and induces cell death in A549 lung cancer cells
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DOI：
10.1016/j.bmc.2005.12.035
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发表时间：
2006-05-01
影响因子：
3.5
通讯作者：
Miao, JY
中科院分区：
文献类型：
--
作者：
Fan, CD;Wang, WW;Miao, JY
为了研究二磷酸氯喹（CQ）对肺癌细胞生长的影响，我们用不同浓度（0.25-128μM）的药物处理A549细胞（肺癌细胞系）24-72小时。结果表明，较低浓度（0.25 至 32 μM）CQ 抑制 A549 细胞的生长，同时诱导空泡形成，并增加酸性室 (VAC) 体积。另一方面，在较高浓度（64-128μM）下，CQ在24小时诱导细胞凋亡，但其诱导空泡形成的作用下降。乳酸脱氢酶(LDH)测定显示，CQ 32-64 μM处理72 h或128 μM处理48 h，CQ可诱导A549细胞坏死。为了了解 CQ 在 A549 细胞中作用的可能机制，我们在 D609（一种磷脂酰胆碱特异性磷脂酶 C 的特异性抑制剂）存在下进一步将细胞与浓度为 32 或 128 μM 的该药物一起孵育。结果表明，D609（50μM）可以抑制CQ 32μM对活力和VAC的影响，但不能改变CQ 128μM对活力和VAC的影响。我们的数据表明，CQ 在较低浓度下通过增加溶酶体的体积来抑制 A549 Icing 癌细胞的生长，并且 PC-PLC 可能参与了这一过程。数据还表明，在较高浓度下，CQ会诱导细胞凋亡和坏死，但此时其增加溶酶体体积的能力逐渐下降，而PC-PLC可能与该过程无关。 (c) 2006 Elsevier Ltd. 保留所有权利。
To investigate the effects of chloroquine diphosphate (CQ) on lung cancer cell growth, we treated A549 cells, it lung cancer cell line, with the drug at various concentrations (0.25-128 mu M) for 24-72 h. The results showed that, at lower concentrations (from 0.25 to 32 mu M) CQ inhibited the growth of A549 cells and, at the same time, it induced vacuolation with increased volume of acidic compartments (VAC). On the other hand, at higher concentrations (64-128 mu M), CQ induced apoptosis at 24 h, while its effect of inducing vacuolation declined. The lactate dehydrogenase (LDH) assay showed that with the treatment of CQ 32-64 mu M for 72 h or 128 mu M for 48 h, CQ induced necrosis of A549 cells. To understand the possible mechanism by which CQ acts in A549 cells, we further incubated the cells with this drug at the concentrations of 32 or 128 mu M in the presence of D609, a specific inhibitor of phosphadylcholine-specific phospholipase C (PC-PLC). The results showed that D609 (50 mu M) could inhibit the effects of CQ 32 mu M on the viability and VAC, but it could not change the effects of CQ 128 mu M on the same. Our data suggested that CQ inhibited A549 Icing cancer cell growth at lower concentrations by increasing the volume of lysosomes and that PC-PLC might be involved in this process. The data also indicated that, at higher concentrations, CQ induced apoptosis and necrosis, but at this time its ability to increase the Volume of lysosome gradually declined, and PC-PLC might not be implicated in the process. (c) 2006 Elsevier Ltd. All rights reserved.