Pigment epithelium‑derived factor inhibits caveolin‑induced interleukin‑8 gene expression and proliferation of human prostate cancer cells

Matsui,Takanori; Ojima,Ayako; Higashimoto,Yuichiro; Taira,Junichi; Fukami,Kei; Yamagishi,Sho‑Ichi

doi:10.3892/ol.2015.3568

Pigment epithelium‑derived factor inhibits caveolin‑induced interleukin‑8 gene expression and proliferation of human prostate cancer cells

Authors:
- Takanori Matsui
- Ayako Ojima
- Yuichiro Higashimoto
- Junichi Taira
- Kei Fukami
- Sho‑Ichi Yamagishi
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Affiliations: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume 830‑0011, Japan, Department of Chemistry, Kurume University School of Medicine, Kurume 830‑0011, Japan, Department of Medicine, Kurume University School of Medicine, Kurume 830‑0011, Japan
Published online on: August 4, 2015 https://doi.org/10.3892/ol.2015.3568
Pages: 2644-2648

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Abstract

Caveolin‑1 (Cav), a primary protein component of caveolae, is overexpressed in prostate cancer, thereby promoting growth and metastasis of this tumor. By contrast, pigment epithelium‑derived factor (PEDF) has been shown to inhibit tumor growth and metastasis, including that of prostate cancer, via its anti‑angiogenic and anti‑inflammatory effects. Although it was recently demonstrated that PEDF binds to Cav and blocks its pro‑inflammatory actions in endothelial cells, it remains unclear whether PEDF also inhibits the tumor‑promoting effects of Cav in cultured prostate cancer cells. The present study examined the effects of PEDF on cell growth, in addition to the gene expression of interleukin‑8 (IL‑8), which is involved in prostate cancer progression, in the PC‑3 human prostate cancer cell line. Exogenous Cav led to a dose‑dependent upregulation of the mRNA expression of IL‑8 in PC‑3 cells, which was blocked by treatment with 1 or 10 nM PEDF, or following the overexpression of small interfering RNAs directed against Cav. Cav (10 nM) increased DNA synthesis in PC‑3 cells, which was again suppressed by the administration of 10 nM PEDF. The results of the present study indicated that PEDF may inhibit Cav‑induced increases in IL‑8 gene expression and proliferation of PC‑3 cells. Therefore, the suppressive effects of PEDF in prostate cancer may, in part, be ascribed to its inhibitory actions on Cav.

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