https://scholars.lib.ntu.edu.tw/handle/123456789/144295
標題: | Recombinant viral protein promotes apoptosis and suppresses invasion of ovarian adenocarcinoma cells by targeting alpha 5 beta 1 integrin to down-regulate Akt and MMP-2 | 作者: | Peng, Jei-Ming Chen, Yee-Hsiung Hung, Shao-Wen Chiu, Ching-Feng Ho, Ming-Yi Lee, Yi-Jen Lai, Tsung-Ching Hsiao, Michael Liang, Chi-Ming Liang, Shu-Mei |
關鍵字: | apoptosis; chemotherapeutic agent; integrin; metastasis; ovarian cancer | 公開日期: | 2012 | 卷: | 165 | 期: | 2 | 起(迄)頁: | 479-493 | 來源出版物: | BRITISH JOURNAL OF PHARMACOLOGY | 摘要: | Background and Purpose As prognosis for patients with metastatic ovarian cancer is generally poor, advances in treatment are needed. Here, we studied the mechanism of action of a recombinant viral capsid protein (rVP1) and explored its effect against ovarian tumour growth and metastasis in vivo. Experimental Approach The human ovarian cancer cell line SKOV3 and BALB/cAnN-Foxn1 female nude mice were used. Effects of rVP1 on the viability, invasive ability, matrix metalloproteinase (MMP)-2 activity and cancer cell proliferation and metastasis were determined by cell proliferation assay, Matrigel invasion assay, gelatin zymographic analysis, as well as bioluminescence imaging and immunohistological analysis in xenograft mouse models respectively. Levels of total and phosphorylated focal adhesion kinase (FAK), PKB/Akt, phosphatase and tensin homologue (PTEN) and glycogen synthase kinase-3β (GSK-3β) were detected by Western blotting. Key Results rVP1 promoted apoptosis and decreased invasion of human ovarian cancer cells. This effect of rVP1 was accompanied by activation of PTEN and GSK-3β as well as down-regulation 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 shown by bioluminescence imaging of mice and immunohistochemical analysis. Conclusion and Implications These results indicate that negative regulation of Akt signalling and MMP-2 by rVP1 may have the potential to suppress ovarian tumour growth and metastasis in vivo. ? 2011 The Authors. British Journal of Pharmacology ? 2011 The British Pharmacological Society. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/243338 | DOI: | 10.1111/j.1476-5381.2011.01581.x | SDG/關鍵字: | focal adhesion kinase; gelatinase A; glycogen synthase kinase 3beta; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; protein kinase B; protein VP1; recombinant protein VP1; unclassified drug; very late activation antigen 5; animal cell; animal experiment; animal tissue; antineoplastic activity; apoptosis; article; bioluminescence; cancer cell; cancer inhibition; cancer invasion; cell proliferation; cell viability; controlled study; down regulation; drug targeting; enzyme activation; enzyme activity; enzyme phosphorylation; female; human; human cell; immunohistochemistry; metastasis; mouse; nonhuman; ovary adenocarcinoma; priority journal; tumor xenograft; Adenocarcinoma; Animals; Apoptosis; Capsid Proteins; Caspase 3; Cell Line, Tumor; DNA Fragmentation; Female; Humans; Integrin alpha5beta1; Matrix Metalloproteinase 2; Mice; Mice, Nude; Neoplasm Invasiveness; Ovarian Neoplasms; Proto-Oncogene Proteins c-akt; Recombinant Proteins; Xenograft Model Antitumor Assays |
顯示於: | 生化科學研究所 |
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