HIV-1 viral protein R (Vpr) induction of apoptosis and cell cycle arrest in multidrug-resistant colorectal cancer cells

  • Authors:
    • Bo Ma
    • Hanchao Zhang
    • Jinhuan Wang
    • Biao Zhang
    • Xinnv Xu
    • Binglu Cheng
  • View Affiliations

  • Published online on: April 23, 2012     https://doi.org/10.3892/or.2012.1782
  • Pages: 358-364
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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.

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July 2012
Volume 28 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Ma B, Zhang H, Wang J, Zhang B, Xu X and Cheng B: HIV-1 viral protein R (Vpr) induction of apoptosis and cell cycle arrest in multidrug-resistant colorectal cancer cells. Oncol Rep 28: 358-364, 2012.
APA
Ma, B., Zhang, H., Wang, J., Zhang, B., Xu, X., & Cheng, B. (2012). HIV-1 viral protein R (Vpr) induction of apoptosis and cell cycle arrest in multidrug-resistant colorectal cancer cells. Oncology Reports, 28, 358-364. https://doi.org/10.3892/or.2012.1782
MLA
Ma, B., Zhang, H., Wang, J., Zhang, B., Xu, X., Cheng, B."HIV-1 viral protein R (Vpr) induction of apoptosis and cell cycle arrest in multidrug-resistant colorectal cancer cells". Oncology Reports 28.1 (2012): 358-364.
Chicago
Ma, B., Zhang, H., Wang, J., Zhang, B., Xu, X., Cheng, B."HIV-1 viral protein R (Vpr) induction of apoptosis and cell cycle arrest in multidrug-resistant colorectal cancer cells". Oncology Reports 28, no. 1 (2012): 358-364. https://doi.org/10.3892/or.2012.1782