Open Access

Antitumor effect of sunitinib in human prostate cancer cells functions via autophagy

  • Authors:
    • Bangqi Wang
    • Dongyuan Lu
    • Min Xuan
    • Weilie Hu
  • View Affiliations

  • Published online on: February 20, 2017     https://doi.org/10.3892/etm.2017.4134
  • Pages: 1285-1294
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to explore sunitinib-induced autophagic effects and the specific molecular mechanisms involved, in vitro, using PC‑3 and LNCaP human prostate cancer cell lines. Cells were exposed to escalating doses of sunitinib treatment and subsequent cell viability and cell cycle analyses were performed to evaluate the inhibitory effect of sunitinib in vitro. Immunofluorescence staining of microtubule associated protein 1A/1B‑light chain 3 (LC3) puncta was employed to assess autophagy levels after sunitinib treatment. Western blot analysis was performed to evaluate variations in the levels of LC3, sequestosome‑1, extracellular signal regulated kinase 1/2 (ERK1/2), mammalian target of rapamycin (mTOR), p70 ribosomal protein S6 kinase (p70S6K) and cleaved caspase‑3 proteins. The present study revealed that sunitinib treatment inhibited cell growth and triggered autophagy in a dose‑dependent manner in both cell lines. In addition, sunitinib activated ERK1/2 and inhibited mTOR/p70S6K signaling. Sunitinib‑induced autophagy was notably reversed by ERK1/2 kinase inhibitor, U0126. Furthermore, inhibition of sunitinib‑induced autophagy by 3-methyladenine enhanced apoptosis and exhibited improved cell viability, which indicated that sunitinib induces not only apoptosis but also autophagic cell death in prostate cancer cell lines. These results may lead to an improved understanding of the mechanism of sunitinib's cytotoxic action and may provide evidence that combined sunitinib autophagy-regulating treatment may be of benefit to anti-prostate cancer therapy.
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April-2017
Volume 13 Issue 4

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

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Spandidos Publications style
Wang B, Lu D, Xuan M and Hu W: Antitumor effect of sunitinib in human prostate cancer cells functions via autophagy. Exp Ther Med 13: 1285-1294, 2017.
APA
Wang, B., Lu, D., Xuan, M., & Hu, W. (2017). Antitumor effect of sunitinib in human prostate cancer cells functions via autophagy. Experimental and Therapeutic Medicine, 13, 1285-1294. https://doi.org/10.3892/etm.2017.4134
MLA
Wang, B., Lu, D., Xuan, M., Hu, W."Antitumor effect of sunitinib in human prostate cancer cells functions via autophagy". Experimental and Therapeutic Medicine 13.4 (2017): 1285-1294.
Chicago
Wang, B., Lu, D., Xuan, M., Hu, W."Antitumor effect of sunitinib in human prostate cancer cells functions via autophagy". Experimental and Therapeutic Medicine 13, no. 4 (2017): 1285-1294. https://doi.org/10.3892/etm.2017.4134