Synergistic antitumor effect of suberoylanilide hydroxamic acid and cisplatin in osteosarcoma cells

Hou,Mengyi; Huang,Zhenglan; Chen,Sicheng; Wang,Hao; Feng,Tianyu; Yan,Shujuan; Su,Yuxi; Zuo,Guowei

doi:10.3892/ol.2018.9224

Synergistic antitumor effect of suberoylanilide hydroxamic acid and cisplatin in osteosarcoma cells

Authors:
- Mengyi Hou
- Zhenglan Huang
- Sicheng Chen
- Hao Wang
- Tianyu Feng
- Shujuan Yan
- Yuxi Su
- Guowei Zuo
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Affiliations: Key Laboratory of Diagnostic Medicine Designated by The Chinese Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, P.R. China, Department of Clinical Medicine, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China, Key Laboratory of Child Development and Disorders of Ministry of Education, Department II of Orthopedics, The Children's Hospital of Chongqing Medical University, Chongqing 400014, P.R. China
Published online on: July 27, 2018 https://doi.org/10.3892/ol.2018.9224
Pages: 4663-4670

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Abstract

Cisplatin, as a first‑line chemotherapy drug, has been widely applied for therapy of osteosarcoma. However, its application is limited by drug resistance and serious side effects, including nephrotoxicity and ototoxicity. Suberoylanilide hydroxamic acid (SAHA) is a newly developed histone deacetylase (HDAC) inhibitor, which is the first Food and Drug Administration‑approved HDAC inhibitor for the treatment of cutaneous manifestations of T‑cell lymphoma. However, SAHA as a monotherapy was revealed to be limited, particularly in solid tumors. In the present study, 143B osteosarcoma cells were treated with multiple concentrations of SAHA or cisplatin, either alone or combined. The morphological characteristics of the treated cells were observed using an inverted microscope. The cytotoxicity effects of the combination of SAHA and cisplatin on 143B cells were analyzed by MTT assay, colony formation assay, wound healing cell migration assay, cell apoptosis assay and cell cycle analysis. Western blot analysis was performed to detect the protein expression levels of B cell lymphoma‑2 (Bcl‑2)‑associated X protein (Bax), Bcl‑2, cleaved‑caspase‑3, cleaved‑caspase‑8 and cleaved‑poly (ADP‑ribose) polymerase (PARP). The experimental data indicated that the inhibition of cell proliferation in the combination group was significantly increased compared with that in single drug groups. Expression levels of pro‑apoptotic protein were upregulated, whereas anti‑apoptotic Bcl‑2 was downregulated significantly in 143B cells following SAHA/cisplatin treatment. Taken together, the results revealed that the combination of SAHA and cisplatin inhibited the proliferation of 143B cells and induced their apoptosis synergistically, and this effectiveness may be mediated by caspase activation.

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