Sodium butyrate enhances the growth inhibitory effect of sunitinib in human renal cell carcinoma cells

  • Authors:
    • Hiromi Sato
    • Miaki Uzu
    • Tatsuro Kashiba
    • Rina Suzuki
    • Takuya Fujiwara
    • Hiroko Okuzawa
    • Koichi Ueno
  • View Affiliations

  • Published online on: May 19, 2017     https://doi.org/10.3892/ol.2017.6217
  • Pages: 937-943
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Abstract

Sunitinib (SU) is a small molecule that inhibits the receptor tyrosine kinase (RTK) signaling pathway, and has been clinically used to treat advanced renal cell carcinoma (RCC). However, SU is not always effective as RCC is a highly chemoresistant type of cancer. One of the factors that confer chemoresistance to RCC is a hypoxic condition. Lack of oxygen activates hypoxia‑inducible factor (HIF) protein, which is followed by the upregulation of growth factors, including vascular endothelial growth factor and activation of the RTK signaling pathway. In this context, histone deacetylase inhibitors (HDACIs) are considered prominent combined agents for SU as they downregulate the expression of HIFs. Therefore, the present study aimed to investigate the effectiveness of combined treatment with SU and sodium butyrate (NaBu), an HDACI. Long‑term exposure to these agents exerted a stronger growth inhibitory effect in RCC cell lines compared with single treatment groups. Furthermore, combined treatment suppressed HIF‑2α protein, which was induced under hypoxic conditions. In addition, this combination sustained the activity of the RTK signaling pathway to the level of intact cells, although a single treatment with SU or NaBu was demonstrated to increase this activity. Overall, it is suggested that the combination of SU and NaBu is effective for overcoming drug resistance in RCC.
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July-2017
Volume 14 Issue 1

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

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Spandidos Publications style
Sato H, Uzu M, Kashiba T, Suzuki R, Fujiwara T, Okuzawa H and Ueno K: Sodium butyrate enhances the growth inhibitory effect of sunitinib in human renal cell carcinoma cells. Oncol Lett 14: 937-943, 2017
APA
Sato, H., Uzu, M., Kashiba, T., Suzuki, R., Fujiwara, T., Okuzawa, H., & Ueno, K. (2017). Sodium butyrate enhances the growth inhibitory effect of sunitinib in human renal cell carcinoma cells. Oncology Letters, 14, 937-943. https://doi.org/10.3892/ol.2017.6217
MLA
Sato, H., Uzu, M., Kashiba, T., Suzuki, R., Fujiwara, T., Okuzawa, H., Ueno, K."Sodium butyrate enhances the growth inhibitory effect of sunitinib in human renal cell carcinoma cells". Oncology Letters 14.1 (2017): 937-943.
Chicago
Sato, H., Uzu, M., Kashiba, T., Suzuki, R., Fujiwara, T., Okuzawa, H., Ueno, K."Sodium butyrate enhances the growth inhibitory effect of sunitinib in human renal cell carcinoma cells". Oncology Letters 14, no. 1 (2017): 937-943. https://doi.org/10.3892/ol.2017.6217