SM‑164 enhances the antitumor activity of adriamycin in human U2‑OS cells via downregulation of X‑linked inhibitor of apoptosis protein

Chen,Jiangwei; Chen,Xuanyin; Chen,Xiaodong; Sun,Haiying; Yang,Dong

doi:10.3892/mmr.2019.10181

SM‑164 enhances the antitumor activity of adriamycin in human U2‑OS cells via downregulation of X‑linked inhibitor of apoptosis protein

Authors:
- Jiangwei Chen
- Xuanyin Chen
- Xiaodong Chen
- Haiying Sun
- Dong Yang
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Affiliations: Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangxi 210009, P.R. China
Published online on: April 22, 2019 https://doi.org/10.3892/mmr.2019.10181
Pages: 5079-5086
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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