Open Access

Icariin enhances the chemosensitivity of cisplatin‑resistant ovarian cancer cells by suppressing autophagy via activation of the AKT/mTOR/ATG5 pathway

  • Authors:
    • Shaoyan Jiang
    • Hong Chang
    • Shaojie Deng
    • Danyi Fan
  • View Affiliations

  • Published online on: April 15, 2019     https://doi.org/10.3892/ijo.2019.4785
  • Pages: 1933-1942
  • Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Icariin is a flavonoid derived from Epimedium sagittatum, and has a wide range of biological and pharmacological effects; however, little is known regarding its effect on drug‑resistant ovarian cancer and the signal transduction pathways underlying the regulation of apoptosis and autophagy. The present study aimed to investigate the re‑sensitization effects of icariin exerted on an ovarian cancer cell line. Autophagy was analyzed in a SKVCR cell line that had been treated with icariin. We investigated the sensitivity of SKVCR cells to cisplatin, as well as the effects of an autophagy agonist (rapamycin) on autophagy, apoptosis, and the protein kinase B (AKT) signaling pathway. Finally, the mechanism underlying the effects of autophagy‑related (ATG) protein ATG5 overexpression on autophagy, apoptosis and AKT signaling in SKVCR cells were determined. The results revealed that treatment with icariin inhibited cell viability and autophagy, but promoted G0/G1 phase cell cycle arrest and apoptosis as determined by Cell Counting Kit‑8, immunofluorescence and flow cytometry assays, respectively. Icariin reduced the resistance of SKVCR cells to cisplatin in vitro by inducing G1/S cell cycle transition, apoptosis and inhibiting autophagy. Furthermore, enhanced autophagy induced by rapamycin treatment or overexpression of ATG5 partially reversed the effect of icariin on cisplatin resistance and autophagy in SKVCR cells. At the molecular level, rapamycin treatment or overexpression of ATG5 reversed the effects of icariin on the expression of autophagy‑associated proteins, including microtubule‑associated protein 1 light chain 3β, Beclin‑1, ATG5 and p62, and the AKT/mammalian target of rapamycin (mTOR) pathway. Collectively, our results suggested that icariin enhances the chemosensitivity of SKVCR cells by suppressing autophagy via activation of the AKT/mTOR signaling pathway.

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June 2019
Volume 54 Issue 6

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Copy and paste a formatted citation
APA
Jiang, S., Chang, H., Deng, S., & Fan, D. (2019). Icariin enhances the chemosensitivity of cisplatin‑resistant ovarian cancer cells by suppressing autophagy via activation of the AKT/mTOR/ATG5 pathway. International Journal of Oncology, 54, 1933-1942. https://doi.org/10.3892/ijo.2019.4785
MLA
Jiang, S., Chang, H., Deng, S., Fan, D."Icariin enhances the chemosensitivity of cisplatin‑resistant ovarian cancer cells by suppressing autophagy via activation of the AKT/mTOR/ATG5 pathway". International Journal of Oncology 54.6 (2019): 1933-1942.
Chicago
Jiang, S., Chang, H., Deng, S., Fan, D."Icariin enhances the chemosensitivity of cisplatin‑resistant ovarian cancer cells by suppressing autophagy via activation of the AKT/mTOR/ATG5 pathway". International Journal of Oncology 54, no. 6 (2019): 1933-1942. https://doi.org/10.3892/ijo.2019.4785