Insulin-like growth factor binding protein-3 mediates interleukin-24-induced apoptosis through inhibition of the mTOR pathway in prostate cancer

IGF-binding protein-3 (IGFBP-3) has been shown to induce apoptosis in an insulin-like growth factor (IGF)-independent manner in various cell systems, however, the underlying molecular mechanisms remain unknown. In the present study, we showed that IGFBP-3 significantly enhanced interleukin-24 (IL-24)-induced cell death in prostate cancer (PC) cell lines in vitro. Both the addition of IGFBP-3 to cell medium or the enforced expression of IGFBP-3 in the PC cell line inhibited activation of mammalian target of rapamycin (mTOR). Downregulation of mTOR/S6K reduced Mcl-1 protein expression and consequently promoted sensitization to IL-24 treatment. Overexpression of Mcl-1 reduced the level of cleaved poly(ADP-ribose) polymerase (PARP) induced by IL-24 and IGFBP-3, suggesting that the IL-24-induced apop-tosis is realized by way of Mcl-1. We then showed that the combination of IL-24 and IGFBP-3 significantly suppressed PC tumor growth in vivo. We propose that the IGFBP-3 and IL-24 non-toxic mTOR inhibitors can be used as an adjuvant in the treatment of PC.

• Publication year

  2015

• Venue

  Oncology Report

• Publication date

  2015-08-13

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3892/or.2015.4201PMID 26323436PMCID 4583521
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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