PMID: 20647689Jul 22, 2010Paper

Hypoxia-response plasmid vector producing bcl-2 shRNA enhances the apoptotic cell death of mouse rectum carcinoma

Journal of Pharmacological Sciences
Takashi FujiokaShigehiro Ohdo

Abstract

Hypoxia-induced gene expression frequently occurs in malignant solid tumors because they often have hypoxic areas in which circulation is compromised due to structurally disorganized blood vessels. Hypoxia-response elements (HREs) are responsible for activating gene transcription in response to hypoxia. In this study, we constructed a hypoxia-response plasmid vector producing short hairpin RNA (shRNA) against B-cell leukemia/lymphoma-2 (bcl-2), an anti-apoptotic factor. The hypoxia-response promoter was made by inserting tandem repeats of HREs upstream of cytomegalovirus (CMV) promoter (HRE-CMV). HRE-CMV shbcl-2 vector consisted of bcl-2 shRNA under the control of HRE-CMV promoter. In hypoxic mouse rectum carcinoma cells (colon-26), the production of bcl-2 shRNA driven by HRE-CMV promoter was approximately 2-fold greater than that driven by CMV promoter. A single intratumoral (i.t.) injection of 40 microg HRE-CMV shbcl-2 to colon-26 tumor-bearing mice caused apoptotic cell death, and repetitive treatment with HRE-CMV shbcl-2 (40 microg/mouse, i.t.) also significantly suppressed the growth of colon-26 tumor cells implanted in mice. Apoptotic and anti-tumor effects were not observed in tumor-bearing mice treated with CMV shbcl-2....Continue Reading

References

Jan 20, 1995·The Journal of Biological Chemistry·G L Wang, G L Semenza
Jul 8, 1998·Proceedings of the National Academy of Sciences of the United States of America·L E HuangH F Bunn
Feb 26, 1999·The Journal of Biological Chemistry·P J KallioL Poellinger
Apr 12, 2000·Proceedings of the National Academy of Sciences of the United States of America·C H SutterG L Semenza
Apr 18, 2002·Genes & Development·Patrick J PaddisonDouglas S Conklin
Sep 24, 2002·Nature Biotechnology·Haibin XiaBeverly L Davidson
Mar 26, 2003·Cell Death and Differentiation·S NagataH Fukuyama
Apr 3, 2003·Genes & Development·Ming Jiang, Jo Milner
Dec 10, 2003·Cancer Science·Shinae Kizaka-KondohMasahiro Hiraoka
Dec 31, 2004·Cell Research·Fischer L Tan, James Q Yin
Dec 13, 2005·Gene Therapy·S I PaiT-C Wu
Apr 11, 2006·Journal of Drug Targeting·Lan-Fang FengDuan-Fang Liao
Apr 26, 2006·Molecular Biology Reports·Jing YuanNing Li
Jul 4, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·George L Sen, Helen M Blau
Feb 24, 2007·Pharmacology & Therapeutics·Pedro Gonzalez-Alegre
Feb 27, 2007·Oncogene·J M Adams, S Cory
Apr 3, 2007·The Journal of Gene Medicine·Danny AllenG Jane Farrar
Aug 19, 2008·The International Journal of Biochemistry & Cell Biology·Valentina BattagliaAntonio Toninello

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Citations

Oct 13, 2015·Apoptosis : an International Journal on Programmed Cell Death·Yongmei CaoYingchuan Li

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