Study of the Cancer Suppressive Effect of a Recombinant Viral Protein in Cancer Cells

• Main Authors: Jei-Ming Peng, 彭瑞銘
• Other Authors: 陳義雄
• Format: Others
• Language: zh-TW
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/66132435579666471339

博士 === 國立臺灣大學 === 生化科學研究所 === 99 === VP1, a capsid protein of Foot-and-mouth disease virus (FMDV), binds to cellular integrins through an arginine-glycine-aspartic acid motif. It is unclear, however, what kind of cellular event(s) is triggered after the binding of VP1 to the cells. First of all, we found that aqueous soluble recombinant DNA derived VP1 (rVP1) of FMDV induced apoptosis in BHK-21 cells after binding to integrins. In addition, treatment of BHK-21 cells with rVP1 resulted in deactivating Akt, and enhancing several pro-apoptotic responses, such as dephosphorylation of GSK-3β and cleavage of procaspase -3, -7 and -9. We also illustrated that the rVP1 treatment caused apoptosis of cancer cells including human breast carcinoma (MCF-7, T-47D, MDA-MB-231), human prostate cancer (22Rv1, PC-3) and human ovarian cancer (SKOV3, OVCAR-3, TOV-21G). As prognosis for patients with metastatic ovarian cancer is generally poor, advances in treatments are needed. We have studied the effect of rVP1 on ovarian tumor growth and metastasis in vivo. We showed that rVP1 promoted the apoptosis of human ovarian cancer cells and decreased the cell invasion. This effect of rVP1 was accompanied by the activation of PTEN and GSK-3β as well as downregulation of FAK, Akt and MMP-2. Anti-integrin antibodies or overexpression of constitutively active Akt reversed the cellular effects of rVP1. Orthotopic and intraperitoneal xenograft mouse models demonstrated that rVP1 attenuated survival and metastasis of human ovarian cancer SKOV3 cell line in vivo through selective regulation of Akt and GSK-3β activity as revealed by bioluminescence imaging of mice and immunohistochemical analysis. These results indicate that negative regulation of Akt signaling and MMP-2 by rVP1 may have the potential to suppress ovarian tumor growth and metastasis in vivo.