Arsenic trioxide inhibits growth of human chondrosarcoma cells through G2/M arrest and apoptosis as well as autophagy
Arsenic trioxide inhibits growth of human chondrosarcoma cells through G2/M arrest and apoptosis as well as autophagy
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三氧化二砷通过 G2/M 期阻滞、细胞凋亡以及自噬抑制人软骨肉瘤细胞的生长
DOI：
10.1007/s13277-015-3040-z
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发表时间：
2015-05-01
期刊：
影响因子：
--
通讯作者：
Yang, Kang
中科院分区：
文献类型：
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作者：
Jiao, Guangjun;Ren, Tingting;Yang, Kang
研究表明Gli 1在软骨肉瘤中表达，而在正常关节软骨组织中不表达。通过小干扰RNA下调Gli 1抑制软骨肉瘤细胞的生长。三氧化二砷（ATO）已被证明通过靶向Gli 1抑制人类癌细胞生长。本研究旨在探讨ATO对软骨肉瘤细胞增殖能力的影响。通过MTT法和集落形成实验，我们发现ATO对软骨肉瘤细胞的生长具有剂量依赖性和时间依赖性的抑制作用。此外，ATO处理诱导SW 1353细胞凋亡，并促进G2/M期阻滞通过流式细胞术分析和蛋白质印迹分析。此外，我们观察到ATO还通过调节哺乳动物雷帕霉素靶蛋白（mTOR）磷酸化来触发自噬。最后，我们发现ATO介导的细胞死亡可以通过自噬抑制剂来避免。综上所述，本研究表明ATO通过促进G2/M期阻滞和诱导细胞凋亡以及自噬对人软骨肉瘤细胞具有治疗功效。ATO给药可能是治疗软骨肉瘤的一种新的治疗策略。
It has been demonstrated that Gli1 is expressed in chondrosarcoma but not in the normal articular cartilage tissues. Downregulating Gli1 by small interfering RNA inhibited chondrosarcoma cells growth. Arsenic trioxide (ATO) has been demonstrated to suppress human cancer cell growth by targeting Gli1. The aim of this study was to investigate the effect of ATO on antineoplastic capability of chondrosarcoma cells. We found that ATO inhibited the growth of chondrosarcoma cells in dose-dependent and time-dependent manners via MTT and colony formation assays. In addition, ATO treatment induced apoptosis and promoted G2/M phase arrest in SW1353 cells as analyzed by flow cytometry assays and Western blotting. Furthermore, we observed that ATO also triggered autophagy by regulating mammalian target of rapamycin (mTOR) phosphorylation. Finally, we found that ATO-mediated cell death could be averted by autophagy inhibitor. Taken together, the current study suggested that ATO had therapeutic efficacy in human chondrosarcoma cells through the promotion of G2/M arrest and induction of both apoptosis as well as autophagy. ATO administration could be a novel therapeutic strategy for treating chondrosarcomas.