title: HIV-1 viral protein R (Vpr) induction of apoptosis and cell cycle arrest             in multidrug-resistant colorectal cancer cells.
abstract: Colorectal cancer is a significant health problem, and the advanced stages of the disease have a low response rate to chemotherapy and easily acquire chemoresistance. HIV-1 viral protein R (Vpr) has been shown to possess inhibitory effects on various malignant cells in vivo and in vitro. In this study, an Ad-Vpr construct was used to infect the multidrug-resistant human colorectal cancer HCT-8/5-FU(MDR) cell line in vitro for cell viability, apoptosis, gene expression and gene activity using the MTT, flow cytometry, immunoblotting and gel shift assays, respectively. The data showed that Ad-Vpr significantly reduced HCT-8/5-FU(MDR) cell viability in a dose- and time-dependent manner. Ad-Vpr infection promoted HCT-8/5-FU(MDR) cells to undergo apoptosis and to arrest at the G2 phase of the cell cycle. The G2 cell cycle protein Cyclin B1 accumulated in the cells after Ad-Vpr infection. Furthermore, Ad-Vpr induced activation of caspase-3 and -9, but not caspase-8, in HCT-8/5-FU(MDR) cells. Ad-Vpr suppressed expression of the Bcl-xl protein, but upregulated Bax expression and cytochrome c release from the mitochondria in HCT-8/5-FU(MDR) cells. Ad-Vpr infection also resulted in a time-dependent decrease in nuclear translocation of NF-κB/p65 protein and p65 DNA-binding activity in HCT-8/5-FU(MDR) cells. The data from the current study provide mechanistic insights into understanding the molecular basis and utility of Ad-Vpr as a novel anticancer agent for multidrug resistance in human colorectal cancer.
authors.affiliation: Key Laboratory for Critical Care Medicine of the Ministry of Health, Affiliated Tianjin First Center Hospital, Tianjin Medical University, Tianjin 300192, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Ma
authors.forename: Hanchao
authors.initials: H
authors.lastname: Zhang
authors.forename: Jinhuan
authors.initials: J
authors.lastname: Wang
authors.forename: Biao
authors.initials: B
authors.lastname: Zhang
authors.forename: Xinnv
authors.initials: X
authors.lastname: Xu
authors.forename: Binglu
authors.initials: B
authors.lastname: Cheng
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D015179:Colorectal Neoplasms; D019008:Drug Resistance, Neoplasm; D004789:Enzyme Activation; D059565:G2 Phase Cell Cycle Checkpoints; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; D016328:NF-kappa B; D011994:Recombinant Proteins; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514912:vpr protein, Human immunodeficiency virus 1; D020169:Caspases