Downregulation of Bmi1 in breast cancer stem cells suppresses tumor growth and proliferation
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Mathangi Srinivasan1, Dhruba J. Bharali1, Thangirala Sudha1, Maha Khedr1,2, Ian Guest3, Stewart Sell3, Gennadi V. Glinsky4 and Shaker A. Mousa1
1The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA
2Division of Clinical Chemistry and Laboratory Medicine, Department of Clinical Pathology, Ain Shams University, Cairo, Egypt
3Wadsworth Center, New York State Department of Health, Albany, NY, USA
4Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA, USA
Shaker A. Mousa, email: [email protected]
Keywords: Bmi1, breast cancer stem cell, downregulation, PTC 209
Received: May 09, 2016 Accepted: February 20, 2017 Published: March 17, 2017
Targeting cancer stem cells during initial treatment is important to reduce incidence of recurrent disease. Bmi1 has been associated with cancer stem cell self-renewal and aggressive disease. The purpose of this study was to determine the effects of downregulation of Bmi1 in breast cancer stem cells in order to target and eliminate the stem cell population in the tumor mass. Bmi1 was downregulated using two approaches in the mouse breast cancer stem cell line FMMC 419II—a small molecule inhibitor (PTC 209) and stable transfection with a Bmi1 shRNA plasmid. The functional effect of Bmi1 downregulation was tested in vitro and in vivo. Each approach led to decreased Bmi1 expression that correlated with an inhibition of cancer stem cell properties in vitro including cell cycle arrest and reduced mammosphere forming potential, and a decrease in tumor mass in vivo after either intra-tumoral or systemic nanoparticle-targeted delivery of anti-Bmi1. These results show that inhibiting Bmi1 expression in breast cancer stem cells could be important for the complete elimination of tumor and potentially preventing disease relapse.
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