Chloroquine and hydroxychloroquine inhibit bladder cancer cell growth by targeting basal autophagy and enhancing apoptosis
Chloroquine and hydroxychloroquine inhibit bladder cancer cell growth by targeting basal autophagy and enhancing apoptosis
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DOI：
10.1016/j.kjms.2017.01.004
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发表时间：
2017-05-01
影响因子：
3.3
通讯作者：
Hwang, Thomas I-Sheng
中科院分区：
文献类型：
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作者：
Lin, Yi-Chia;Lin, Ji-Fan;Hwang, Thomas I-Sheng
氯喹（CQ）和羟氯喹（HCQ）是两种具有潜在抗癌活性的抗疟药。本研究通过体外细胞自噬抑制和细胞凋亡诱导两方面研究了CQ和HCQ对膀胱癌细胞生长的影响。结果表明，CQ和HCQ以时间和剂量依赖性方式抑制多种人膀胱细胞系（包括RT 4，5637和T24）的增殖，特别是与永生化尿路上皮细胞（SV-Huc-1）或其他参考癌细胞系（PC 3和MCF-7）相比，在晚期膀胱癌细胞系（5637和T24）中。我们发现，与SV-Huc-1相比，CQ或HCQ处理24小时显著降低了5637和T24细胞中的克隆形成。由于人膀胱癌肿瘤表现出高基础水平的自噬活性，我们检测了用CQ和HCQ处理的细胞中的自噬通量，显示了CQ或HCQ处理的细胞中LC 3通量的交替。此外，CQ和HCQ处理的膀胱癌细胞发生凋亡，导致caspase 3/7活性增加，裂解的聚（ADP-核糖）聚合酶（PARP），caspase 3和DNA片段化水平增加。鉴于这些结果，用CQ和HCQ靶向自噬代表了针对人膀胱癌的有效癌症治疗策略。版权所有（C）2017，高雄医学大学.出版社：Elsevier Taiwan LLC
Chloroquine (CQ) and hydroxychloroquine (HCQ), two antimalarial drugs, are suggested to have potential anticancer properties. in the present study, we investigated the effects of CQ and HCQ on cell growth of bladder cancer with emphasis on autophagy inhibition and apoptosis induction in vitro. The results showed that CQ and HCQ inhibited the proliferation of multiple human bladder cell lines (including RT4, 5637, and T24) in a time- and dose-dependent fashion, especially in advanced bladder cancer cell lines (5637 and T24) compared to immortalized uroepithelial cells (SV-Huc-1) or other reference cancer cell lines (PC3 and MCF-7). We found that 24-hour treatment of CQ or HCQ significantly decreased the clonogenic formation in 5637 and T24 cells compared to SV-Huc-1. As human bladder cancer tumor exhibits high basal level of autophagic activities, we detected the autophagic flux in cells treated with CQ and HCQ, showing an alternation in LC3 flux in CQ- or HCQ-treated cells. Moreover, bladder cancer cells treated with CQ and HCQ underwent apoptosis, resulting in increased caspase 3/7 activities, increased level of cleaved poly(ADP-ribose) polymerase (PARP), caspase 3, and DNA fragmentation. Given these results, targeting autophagy with CQ and HCQ represents an effective cancer therapeutic strategy against human bladder cancer. Copyright (C) 2017, Kaohsiung Medical University. Published by Elsevier Taiwan LLC.