Open Access

Efficacy of celastrol combined with cisplatin in enhancing the apoptosis of U‑2OS osteosarcoma cells via the mitochondrial and endoplasmic reticulum pathways of apoptosis

  • Authors:
    • Qiang Wang
    • Xiaolong Yu
    • Fan Li
    • Xin Lv
    • Xiaoxing Fu
    • Houyun Gu
    • Hucheng Liu
    • Jun Liu
    • Min Dai
    • Bin Zhang
  • View Affiliations

  • Published online on: February 1, 2019     https://doi.org/10.3892/ol.2019.10007
  • Pages: 3305-3313
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteosarcoma is a common primary malignant tumor of bone, and the poor prognosis and low 5‑year survival rate have not improved for three decades. The present study aimed to study the effect a combination of celastrol and cisplatin on the human osteosarcoma cell line U‑2OS, and to investigate the mechanism by which celastrol/cisplatin induces the apoptosis of osteosarcoma cells. MTT and Annexin V‑FITC/PI assays were used to evaluate the effects of combined celastrol/cisplatin on growth and apoptosis, respectively, in U‑2OS cells. Morphological changes accompanying cell growth inhibition were observed using a fluorescence microscope. Combination index (CI) analysis was used to evaluate the combinatorial effects of celastrol/cisplatin treatment. Western blotting was used to quantify the expression of apoptosis‑associated proteins. It was identified that celastrol/cisplatin inhibited the growth of U‑2OS cells in a dose‑dependent manner. CI analysis revealed that combined celastrol/cisplatin demonstrated a synergistic effect in U‑2OS cells, with CIs ranging from 0.80 to 0.97 at effect levels from IC10 to IC70. In addition, it was observed that celastrol/cisplatin upregulated the expression of Bcl‑associated X protein, cytochrome c, caspase‑3 and C/EBP homologous protein, and downregulated the expression of Bcl‑2, poly(ADP‑ribose) polymerase, 78 kDa glucose‑regulated protein and caspase‑9, whereas the expression of caspase‑8 remained unchanged. To conclude, celastrol/cisplatin induced apoptosis in U‑2OS cells via the mitochondrial and endoplasmic reticulum pathways, particularly in the former. Celastrol/cisplatin therefore exhibits potential as a novel therapeutic combination for the treatment of osteosarcoma.
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March-2019
Volume 17 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Wang Q, Yu X, Li F, Lv X, Fu X, Gu H, Liu H, Liu J, Dai M, Zhang B, Zhang B, et al: Efficacy of celastrol combined with cisplatin in enhancing the apoptosis of U‑2OS osteosarcoma cells via the mitochondrial and endoplasmic reticulum pathways of apoptosis. Oncol Lett 17: 3305-3313, 2019
APA
Wang, Q., Yu, X., Li, F., Lv, X., Fu, X., Gu, H. ... Zhang, B. (2019). Efficacy of celastrol combined with cisplatin in enhancing the apoptosis of U‑2OS osteosarcoma cells via the mitochondrial and endoplasmic reticulum pathways of apoptosis. Oncology Letters, 17, 3305-3313. https://doi.org/10.3892/ol.2019.10007
MLA
Wang, Q., Yu, X., Li, F., Lv, X., Fu, X., Gu, H., Liu, H., Liu, J., Dai, M., Zhang, B."Efficacy of celastrol combined with cisplatin in enhancing the apoptosis of U‑2OS osteosarcoma cells via the mitochondrial and endoplasmic reticulum pathways of apoptosis". Oncology Letters 17.3 (2019): 3305-3313.
Chicago
Wang, Q., Yu, X., Li, F., Lv, X., Fu, X., Gu, H., Liu, H., Liu, J., Dai, M., Zhang, B."Efficacy of celastrol combined with cisplatin in enhancing the apoptosis of U‑2OS osteosarcoma cells via the mitochondrial and endoplasmic reticulum pathways of apoptosis". Oncology Letters 17, no. 3 (2019): 3305-3313. https://doi.org/10.3892/ol.2019.10007