Knockdown of hypoxia-inducible factor-1alpha in breast carcinoma MCF-7 cells results in reduced tumor growth and increased sensitivity to methotrexate

Biochemical and Biophysical Research Communications
Jing LiRobert Chunhua Zhao

Abstract

The hypoxia-inducible factor (HIF) 1alpha is a key regulator of the cellular response to oxygen deprivation. Specific disruption of the HIF-1 pathway is important for exploring its role in tumor biology and developing more efficient weapons to treat cancer. In this study, we stably transfected human breast tumor MCF-7 cells with short hairpin RNA expression vectors targeting HIF-1alpha. After knockdown of HIF-1alpha, hypoxia-induced expression of its target genes such as vascular endothelial growth factor, Glut-1, phosphoglycerate kinase, and P-glycoprotein were markedly attenuated. Moreover, HIF-1alpha knockdown was found to suppress the shift from S-phase to G(1) induced by hypoxia and increase drug sensitivity to methotrexate. The growth rates of HIF1alpha-knockdown tumors were drastically retarded in both subcutaneous and orthotopic xenograft models, which were accompanied by decreased angiogenesis and reduced expression of glucose transporter in tissue sections. These data demonstrate that HIF-1alpha knockdown reduces tumorigenicity of MCF-7 cells and suggest a promising combination of both anti-HIF-1 strategy and traditional chemotherapy to improve cancer treatment.

References

Jun 6, 1995·Proceedings of the National Academy of Sciences of the United States of America·G L WangG L Semenza
Oct 1, 1996·Genome Research·U E GibsonP M Williams
Apr 21, 2001·Molecular and Cellular Biology·T N SeagrovesR S Johnson
Jan 31, 2002·Annual Review of Medicine·Johannes Czernin, Michael E Phelps
Feb 1, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·A FylesR P Hill
Apr 3, 2003·Journal of the National Cancer Institute·Eun-Jin YeoJong-Wan Park
Sep 6, 2003·Cancer Cell·Barbara BlouwGabriele Bergers
Sep 18, 2003·Nature Reviews. Cancer·Gregg L Semenza
Jun 11, 2004·Cell Cycle·Minori Koshiji, L Eric Huang
Apr 26, 2005·International Journal of Cancer. Journal International Du Cancer·Jean-Philippe DalesColette Charpin
May 18, 2005·Biochemical and Biophysical Research Communications·Ying CaoRobert Chunhua Zhao
Aug 16, 2005·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Marianne NordsmarkJens Overgaard

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Citations

Jun 20, 2008·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Tiejun YinChengping Liu
Oct 12, 2012·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·M A KocdorJ Russo
Jan 18, 2011·Stem Cells and Development·Zhao SunRobert Chunhua Zhao
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Beek Y ChinLeo E Otterbein
Apr 7, 2011·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Nadine Rohwer, Thorsten Cramer
Dec 10, 2009·International Journal of Cancer. Journal International Du Cancer·Lili LiuDaiming Fan
Jul 20, 2006·Expert Opinion on Therapeutic Targets·Rachida S Bel AibaThomas Kietzmann
Jan 31, 2015·Oncology Reports·Yoshinori ImamuraHironobu Minami
May 9, 2014·Experimental Biology and Medicine·Shao-Chieh LinShaw-Jenq Tsai
Oct 21, 2018·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Tsung-Lin ChengChao-Han Lai
Jun 15, 2007·Journal of Cellular Physiology·Ana Maria MenesesGareth I Owen
Jul 4, 2009·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·Binzhi TangDezhi Mu
Dec 12, 2012·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Makoto ShimanishiHiroyoshi Hiratsuka
Aug 1, 2019·Journal for Immunotherapy of Cancer·Thuy T TranHarriet M Kluger
May 1, 2018·Cancer Biology & Therapy·Caixia TangYingli Wu
Dec 6, 2020·Cancer Letters·Courtney E McAleeseRodney F Minchin
Jul 18, 2020·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Nuray ErinThomas Efferth
Sep 22, 2010·Biochemical Pharmacology·M Cristina de AlmagroCarlos J Ciudad

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