SM-164 enhances the antitumor activity of adriamycin in human U2-OS cells via downregulation of X-linked inhibitor of apoptosis protein
SM-164 enhances the antitumor activity of adriamycin in human U2-OS cells via downregulation of X-linked inhibitor of apoptosis protein
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SM-164 通过下调 X-连锁凋亡蛋白抑制剂增强阿霉素在人 U2-OS 细胞中的抗肿瘤活性
DOI：
10.3892/mmr.2019.10181
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发表时间：
2019-06-01
影响因子：
3.4
通讯作者：
Yang, Dong
中科院分区：
文献类型：
--
作者：
Chen, Jiangwei;Chen, Xuanyin;Yang, Dong
SM-164和阿霉素(ADM)对人骨肉瘤U2-OS细胞的抗肿瘤作用及其机制尚不清楚。本研究将U2-OS细胞分为对照组、ADM组、SM-164组和ADM+SM-164组。此外，SM-164和ADM同时处理的细胞进一步分为三个亚组：SM-164+ADM组、SM-164+ADM+载体组和SM-164+ADM+X连锁凋亡蛋白抑制物(XIAP)静止组。用shRNA慢病毒载体转染法获得XIAP的表达。逆转录-定量聚合酶链式反应和Western blotting检测caspase-7、-9和-3、聚ADP-核糖聚合酶(PARP)、XIAP、细胞凋亡抑制蛋白-1(CIAP-1)和Survivin的表达。用四甲基偶氮唑盐比色法和流式细胞仪分别检测细胞存活率和细胞凋亡率。与对照组相比，ADM和SM-164处理组细胞存活率降低，细胞凋亡率增加。ADM和SM-164可促进caspase-7、-9、-3和PARP的表达，降低XIAP、Survivin和CIAP-1的表达。与ADM+SM-164组相比，XIAP沉默+ADM+SM-164组进一步降低了细胞存活率，促进了细胞凋亡，增加了caspase-7、-9和-3的表达，增加了PARP的表达，而Survivin和CIAP-1的表达降低。ADM和SM-164联合治疗骨肉瘤可能通过减少XIAP的表达而成为治疗骨肉瘤的潜在药物。
The antitumor effects of SM-164 and adriamycin (ADM) on human osteosarcoma U2-OS cells, the underlying mechanism are yet to be investigated. In the present study, U2-OS cells were divided into control, ADM, SM-164, and ADM + SM-164 groups. In addition, cells treated with both SM-164 and ADM were further divided into three subgroups: SM-164 + ADM, SM-164 + ADM + vector and SM-164 + ADM + X-linked inhibitor of apoptosis protein (XIAP) silencing groups. XIAP expression was achieved via transfection with shRNA lentiviral vectors. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to detect the expression of caspases-7, -9, and -3, poly ADP-ribose polymerase (PARP), XIAP, cellular inhibitor of apoptosis protein-1 (cIAP-1) and survivin. Cell viability and apoptosis were evaluated using MTT and flow cytometry assays, respectively. Compared with the control group, cell viability decreased, while apoptosis was increased in the ADM and SM-164-treatment group. ADM and SM-164 treatment promoted the expression of caspases-7, -9 and -3, and PARP, but reduced the expression of XIAP, survivin and cIAP-1. Compared with ADM + SM-164 group, XIAP silencing with ADM + SM-164 treatment further reduced cell viability, promoted apoptosis, increased caspase-7, -9 and -3, and PARP expression; however the expression of survivin and cIAP-1 were reduced. Combined ADM and SM-164 treatment may be considered as potential therapeutic agent in the treatment of osteosarcoma, possibly via reductions XIAP expression.