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

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 - 1 Nov 2013

Fingerprint

Hypoxia-Inducible Factor 1
Androgens
Prostatic Neoplasms
docetaxel
Cell Line
Small Interfering RNA
Therapeutics
endothelial PAS domain-containing protein 1
Hypoxia
Insulin-Like Growth Factor I
Cell Survival
Protein Isoforms
Western Blotting
Cell Proliferation
Gene Expression
Drug Therapy

Keywords

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

Cite this

@article{b96d1af021844887953c4c705d8442b6,
title = "The role of hypoxia-inducible factor-1α and -2α in androgen insensitive prostate cancer cells",
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.",
keywords = "Hypoxia-inducible factor, Prostate cancer, SiRNA, Zinc",
author = "Jeong, {Chang Wook} and Yoon, {Cheol Yong} and Jeong, {Seong Jin} and Hong, {Sung Kyu} and Seok-Soo Byun and Cheol Kwak and Lee, {Sang Eun}",
year = "2013",
month = "11",
day = "1",
doi = "10.1016/j.urolonc.2012.03.022",
language = "English",
volume = "31",
pages = "1448--1456",
journal = "Urologic Oncology: Seminars and Original Investigations",
issn = "1078-1439",
publisher = "Elsevier Inc.",
number = "8",

}

TY - JOUR

T1 - The role of hypoxia-inducible factor-1α and -2α in androgen insensitive prostate cancer cells

AU - Jeong, Chang Wook

AU - Yoon, Cheol Yong

AU - Jeong, Seong Jin

AU - Hong, Sung Kyu

AU - Byun, Seok-Soo

AU - Kwak, Cheol

AU - Lee, Sang Eun

PY - 2013/11/1

Y1 - 2013/11/1

N2 - 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.

AB - 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.

KW - Hypoxia-inducible factor

KW - Prostate cancer

KW - SiRNA

KW - Zinc

UR - http://www.scopus.com/inward/record.url?scp=84886253579&partnerID=8YFLogxK

U2 - 10.1016/j.urolonc.2012.03.022

DO - 10.1016/j.urolonc.2012.03.022

M3 - Article

C2 - 22537539

AN - SCOPUS:84886253579

VL - 31

SP - 1448

EP - 1456

JO - Urologic Oncology: Seminars and Original Investigations

JF - Urologic Oncology: Seminars and Original Investigations

SN - 1078-1439

IS - 8

ER -