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Effects of Suberoylanilide Hydroxamic Acid Combined with Cisplatin on the Growth, Apoptosis and Migration of Osteosarcoma Cells
Hou Mengyi, Yao Juan, Wang Hao, Zhang Zhang, Yan Shujuan, Zuo Guowei*
Key Laboratory of Medical Diagnostics Founded by Ministry of Education,College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China
Abstract: This work was aimed to investigate the effects of histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) combined with DDP on osteosarcoma cells. The osteosarcoma 143B cells were treated with different concentrations of SAHA or cisplatin, either alone or combined for 48 h. The morphological characteristics of treated cells were observed by inverted microscope. The cytotoxicity effects in single drug group and combination drugs group were observed by MTT assay. The cell apoptosis was quantified by flow cytometry.SAHA or DDP was used either alone or in combination to compare the migration ability with wound healing assay. The colony-forming ability was analyzed by colony formation assay. The expressions of cleaved-Caspase-8,cleaved-PARP were detected by Western blot. The results showed that the necrosis of 143B cells was obvious in SAHA+DDP group. The inhibition of cell proliferation in SAHA+DDP group was significantly higher than those in single drug group. SAHA combined with DDP of middle or low doses showed a synergistic effect, however, SAHA combined with DDP of high dose showed a simple additive effect. The early apoptosis rate of SAHA+DDP group was significantly higher than those of single drug group, and the cell migration rate and the colony-forming ability in SAHA+DDP group were significantly lower than single drug group. The expressions of cleaved-Caspase-8,cleaved-PARP were up-regulaton significantly in 143B cells after SAHA+DDP treatment. The results suggested that SAHA+DDP could inhibit the proliferation and migration, and promote the apoptosis of osteosarcoma 143B cells.In addition, the combination of SAHA and DDP has a synergistic effect.