Recombinant viral protein promotes apoptosis and suppresses invasion of ovarian adenocarcinoma cells by targeting α5β1 integrin to down-regulate Akt and MMP-2

Jei Ming Peng, Yee Hsiung Chen, Shao Wen Hung, Ching Feng Chiu, Ming Yi Ho, Yi Jen Lee, Tsung Ching Lai, Michael Hsiao, Chi Ming Liang, Shu Mei Liang

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)479-493
Number of pages15
JournalBritish Journal of Pharmacology
Volume165
Issue number2
DOIs
Publication statusPublished - Jan 1 2012
Externally publishedYes

Fingerprint

Matrix Metalloproteinase 2
Viral Proteins
Glycogen Synthase Kinase 3
Recombinant Proteins
Integrins
Ovarian Neoplasms
Adenocarcinoma
Down-Regulation
Apoptosis
Neoplasm Metastasis
Focal Adhesion Protein-Tyrosine Kinases
Phosphoric Monoester Hydrolases
Heterografts
Cell Proliferation
Cell Line
Neoplasms
Capsid Proteins
Gelatin
Growth
Nude Mice

Keywords

  • apoptosis
  • chemotherapeutic agent
  • integrin
  • metastasis
  • ovarian cancer

ASJC Scopus subject areas

  • Pharmacology

Cite this

Recombinant viral protein promotes apoptosis and suppresses invasion of ovarian adenocarcinoma cells by targeting α5β1 integrin to down-regulate Akt and MMP-2. / 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.

In: British Journal of Pharmacology, Vol. 165, No. 2, 01.01.2012, p. 479-493.

Research output: Contribution to journalArticle

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. / Recombinant viral protein promotes apoptosis and suppresses invasion of ovarian adenocarcinoma cells by targeting α5β1 integrin to down-regulate Akt and MMP-2. In: British Journal of Pharmacology. 2012 ; Vol. 165, No. 2. pp. 479-493.
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abstract = "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.",
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AU - Chen, Yee Hsiung

AU - Hung, Shao Wen

AU - Chiu, Ching Feng

AU - Ho, Ming Yi

AU - Lee, Yi Jen

AU - Lai, Tsung Ching

AU - Hsiao, Michael

AU - Liang, Chi Ming

AU - Liang, Shu Mei

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AB - 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.

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KW - chemotherapeutic agent

KW - integrin

KW - metastasis

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