Paeonol enhances the sensitivity of human ovarian cancer cells to radiotherapy-induced apoptosis due to downregulation of the phosphatidylinositol-3-kinase/Akt/phosphatase and tensin homolog pathway and inhibition of vascular endothelial growth factor

  • Authors:
    • Hai‑Mei Zhou
    • Qin‑Xiang Sun
    • Yan Cheng
  • View Affiliations

  • Published online on: August 3, 2017     https://doi.org/10.3892/etm.2017.4877
  • Pages: 3213-3220
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Abstract

Radiotherapy is a vital and effective method to treat solid tumors. However, in many tumor types, development of resistance of cancer cells and cytotoxicity in normal tissues presents a major therapeutic problem. It is therefore crucial to identify and develop novel sensitizing agents that may improve the response to radiation therapy without causing any adverse effects. The present study aimed to investigate whether paeonol, a bioactive flavonoid, was able to confer sensitivity to radiation in human ovarian cancer cells. The human ovarian cancer cell lines SKOV‑3 and OVCAR‑3 were exposed to varying doses of radiation (2, 4 or 6 Gy) in the presence or absence of paeonol (25, 50 or 100 µM). Radiosensitivity was assessed by measuring cell viability using a CCK‑8 assay and Annexin V/PI staining. Expression of vascular endothelial growth factor (VEGF), hypoxia inducible factor‑1α (HIF‑1α), proteins of the phosphatidylinositol-3-kinase (PI3K)/Akt pathway and apoptotic pathway proteins [caspase‑3, Bcl‑2‑associated death promoter, B‑cell lymphoma (Bcl)‑2, Bcl‑2‑associated X and Bcl‑extra large (Bcl‑xL)] were also assessed. Paeonol treatment enhanced apoptosis of SKOV‑3 and OVCAR‑3 cells that were exposed to radiation. The expression of Bcl‑2 and Bcl‑xL were markedly upregulated in these cells. Treatment with paeonol concentrations of 50 and 100 µM caused a significant downregulation of VEGF, HIF‑1α and PI3K/Akt pathway proteins. Paeonol effectively enhanced the sensitivity of ovarian cancer cells to radiation by significantly altering regulation of the proteins of the PI3K/Akt pathway, in addition to downregulating VEGF and HIF-1α.

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October-2017
Volume 14 Issue 4

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Zhou HM, Sun QX and Cheng Y: Paeonol enhances the sensitivity of human ovarian cancer cells to radiotherapy-induced apoptosis due to downregulation of the phosphatidylinositol-3-kinase/Akt/phosphatase and tensin homolog pathway and inhibition of vascular endothelial growth factor. Exp Ther Med 14: 3213-3220, 2017
APA
Zhou, H., Sun, Q., & Cheng, Y. (2017). Paeonol enhances the sensitivity of human ovarian cancer cells to radiotherapy-induced apoptosis due to downregulation of the phosphatidylinositol-3-kinase/Akt/phosphatase and tensin homolog pathway and inhibition of vascular endothelial growth factor. Experimental and Therapeutic Medicine, 14, 3213-3220. https://doi.org/10.3892/etm.2017.4877
MLA
Zhou, H., Sun, Q., Cheng, Y."Paeonol enhances the sensitivity of human ovarian cancer cells to radiotherapy-induced apoptosis due to downregulation of the phosphatidylinositol-3-kinase/Akt/phosphatase and tensin homolog pathway and inhibition of vascular endothelial growth factor". Experimental and Therapeutic Medicine 14.4 (2017): 3213-3220.
Chicago
Zhou, H., Sun, Q., Cheng, Y."Paeonol enhances the sensitivity of human ovarian cancer cells to radiotherapy-induced apoptosis due to downregulation of the phosphatidylinositol-3-kinase/Akt/phosphatase and tensin homolog pathway and inhibition of vascular endothelial growth factor". Experimental and Therapeutic Medicine 14, no. 4 (2017): 3213-3220. https://doi.org/10.3892/etm.2017.4877