| HIV-1 viral protein R (Vpr) induction of apoptosis and cell cycle arrest in multidrug-resistant colorectal cancer cells. | |
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MedLine Citation:
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PMID: 22552851 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Bo Ma; Hanchao Zhang; Jinhuan Wang; Biao Zhang; Xinnv Xu; Binglu Cheng |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-4-23 |
Journal Detail:
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Title: Oncology reports Volume: - ISSN: 1791-2431 ISO Abbreviation: - Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-5-3 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9422756 Medline TA: Oncol Rep Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Key Laboratory for Critical Care Medicine of the Ministry of Health, Affiliated Tianjin First Center Hospital, Tianjin Medical University, Tianjin 300192, P.R. China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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