The role of hypoxia-inducible factor-1α and -2α in androgen insensitive prostate cancer cells

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Objectives: The aim of this study was to investigate the effects of induction and knocking down of hypoxia-inducible factor (HIF)-1α and/or -2α on tumor biology in androgen insensitive prostate cancer cell lines. Materials and methods: The induction patterns of HIF-1α and -2α after treatment with ZnSO4 were evaluated in PC3 and DU145 cells. Both cell lines were transfected with siRNA targeted against HIF-1α and/or -2α, and the expression patterns of these 2 HIF isoforms were examined. We next performed cell counting Kit-8 (CCK-8) assays and matrigel invasion assays. Potential additive effects of HIF blockade to chemotherapy (docetaxel) or target agents (sunitinib and sorafenib) were examined. In addition, gene expression changes were determined in ZnSO4-treated DU145 cells using Western blotting. Results: ZnSO4 affected the expression of HIF in a dose-dependent manner. HIF expression was increased within the first 3 hours but then decreased. Cells in which HIF-1α and/or -2α had been knocked down using siRNA showed decreased cell viability. Invasion abilities were increased by ZnSO4 treatment in both cell lines overexpressing HIF. However, invasion potencies were decreased in response to treatment with HIF siRNAs. Blocking HIF prominently augmented the antitumor effects of target agents. The underlying mechanism could be associated with p21, cMET, IGF-1, and GLUT-1. Conclusions: Our results demonstrate that HIF-1α and -2α are important for cell proliferation and invasion ability in prostate cancer. Together, our results indicate that combinations of target agents with HIF knockdown may represent a promising strategy for the treatment of prostate cancer.

Original languageEnglish
Pages (from-to)1448-1456
Number of pages9
JournalUrologic Oncology: Seminars and Original Investigations
Volume31
Issue number8
DOIs
StatePublished - Nov 2013

Keywords

  • Hypoxia-inducible factor
  • Prostate cancer
  • SiRNA
  • Zinc

Fingerprint Dive into the research topics of 'The role of hypoxia-inducible factor-1α and -2α in androgen insensitive prostate cancer cells'. Together they form a unique fingerprint.

Cite this