ABT-737 potentiates cisplatin-induced apoptosis in human osteosarcoma cells via the mitochondrial apoptotic pathway

  • Authors:
    • Fengtian Zhang
    • Xiaolong Yu
    • Xuqiang Liu
    • Tonghua Zhou
    • Tao Nie
    • Ming Cheng
    • Hucheng Liu
    • Min Dai
    • Bin Zhang
  • View Affiliations

  • Published online on: August 14, 2017     https://doi.org/10.3892/or.2017.5909
  • Pages: 2301-2308
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Abstract

ABT-737 is a BH-3 mimetic that inhibits Bcl-2 and induces apoptosis of cancer cells, which has potential for anticancer therapies. Studies have shown that Bcl-2 expression in human osteosarcoma (OS) cells plays a significant role in tumor progression; however, its effects on OS cell apoptosis are still unknown. Therefore, we examined whether ABT-737 was effective in eliminating human U-2OS cells, either alone or in combination with the chemotherapy drug cisplatin [cis-diamminedichloroplatinum (II); DDP]. Furthermore, we studied the molecular mechanisms of ABT-737 in combination with DDP to induce apoptosis. To analyze the role of ABT-737 and/or DDP on osteosarcoma progression, CCK-8 viability assay, flow cytometry, Hoechst 33258 staining, and western blots were performed. Combined use of ABT-737 and DDP synergistically suppressed cell viability and induced apoptosis in human U-2OS cells when compared with either compound treated alone at low doses. We found that the combination of ABT-737 and DDP upregulated the expression of the pro-apoptotic protein Bax and downregulated the expression of the pro-survival protein Bcl-2, resulting in a change in the Bax/Bcl-2 ratio, release of cytochrome c, and activation of the mitochondrial apoptotic pathway, which resulted in caspase-9 and caspase-3 activation and PARP cleavage. Our results demonstrated that ABT-737 alone has a nominal influence on human U-2OS cells when treated within the clinically administered range, but when combined with DDP, it can inhibit the proliferation of human U-2OS cells by inducing apoptosis via the mitochondrial apoptotic pathway.
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October-2017
Volume 38 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Zhang F, Yu X, Liu X, Zhou T, Nie T, Cheng M, Liu H, Dai M and Zhang B: ABT-737 potentiates cisplatin-induced apoptosis in human osteosarcoma cells via the mitochondrial apoptotic pathway. Oncol Rep 38: 2301-2308, 2017.
APA
Zhang, F., Yu, X., Liu, X., Zhou, T., Nie, T., Cheng, M. ... Zhang, B. (2017). ABT-737 potentiates cisplatin-induced apoptosis in human osteosarcoma cells via the mitochondrial apoptotic pathway. Oncology Reports, 38, 2301-2308. https://doi.org/10.3892/or.2017.5909
MLA
Zhang, F., Yu, X., Liu, X., Zhou, T., Nie, T., Cheng, M., Liu, H., Dai, M., Zhang, B."ABT-737 potentiates cisplatin-induced apoptosis in human osteosarcoma cells via the mitochondrial apoptotic pathway". Oncology Reports 38.4 (2017): 2301-2308.
Chicago
Zhang, F., Yu, X., Liu, X., Zhou, T., Nie, T., Cheng, M., Liu, H., Dai, M., Zhang, B."ABT-737 potentiates cisplatin-induced apoptosis in human osteosarcoma cells via the mitochondrial apoptotic pathway". Oncology Reports 38, no. 4 (2017): 2301-2308. https://doi.org/10.3892/or.2017.5909