anti-cancer effect of hiv-1 viral protein r on doxorubicin resistant neuroblastoma抗癌抗hiv - 1病毒蛋白r对阿霉素的影响神经母细胞瘤.pdfVIP

Anti-Cancer Effect of HIV-1 Viral Protein R on Doxorubicin Resistant Neuroblastoma 1,2,3 1 1 1 4 Richard Y. Zhao *, Dong Liang , Ge Li , Christopher W. Larrimore , Bernard L. Mirkin 1 Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America, 2 Department of Microbiology-Immunology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America, 3 Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America, 4 Department of Pediatrics, Children’s Memorial Institute for Education and Research, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America Abstract Several unique biological features of HIV-1 Vpr make it a potentially powerful agent for anti-cancer therapy. First, Vpr inhibits cell proliferation by induction of cell cycle G2 arrest. Second, it induces apoptosis through multiple mechanisms, which could be significant as it may be able to overcome apoptotic resistance exhibited by many cancerous cells, and, finally, Vpr selectively kills fast growing cells in a p53-independent manner. To demonstrate the potential utility of Vpr as an anti-cancer agent, we carried out proof-of-concept studies in vitro and in vivo. Results of our preliminary studies demonstrated that Vpr induces cell cycle G2 arrest and apoptosis in a variety of cancer types. Moreover, the same Vpr effects could also be detected in some cancer cells that are resistant to anti-cancer drugs s