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01-06-2012 | Original Article

The Rho kinase inhibitor fasudil is involved in p53-mediated apoptosis in human hepatocellular carcinoma cells

Authors: Yuko Takeba, Naoki Matsumoto, Minoru Watanabe, Sachiko Takenoshita-Nakaya, Yuki Ohta, Toshio Kumai, Masayuki Takagi, Satoshi Koizumi, Takeshi Asakura, Takehito Otsubo

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2012

Abstract

Purpose

Rho kinase is an important factor in tumor progression. We demonstrated that Rho kinase-associated coil-containing protein kinase (ROCK) is expressed in hepatic tissues in hepatocellular carcinoma (HCC) and confirmed its roles in cell survival in HCC cells using the ROCK inhibitor, fasudil.

Methods

ROCK protein levels were estimated in hepatic tissues with HCC compared with healthy liver tissues or hepatic hemangioma tissues using immunohistochemistry. Furthermore, HepG2 and Huh7 cells were cultured with ROCK inhibitor, fasudil for 24 h in vitro. Cell proliferation was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt assay, and apoptotic cells were detected by cell death ELISA. The expression apoptosis-related proteins were analyzed using Western blotting.

Results

Fasudil significantly decreased cell proliferation and induced apoptosis mediated by increases in p53, Bax, caspase-9, and caspase-3 in HepG2 and Huh7 cells. The induction of apoptosis was inhibited in HCC cells precultured with p53 decoy oligodeoxynucleotide.

Conclusion

These results suggest that ROCK inhibits the p53-mediated apoptosis pathway in HCC. Fasudil may thus be a beneficial approach to HCC therapy.

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Title: The Rho kinase inhibitor fasudil is involved in p53-mediated apoptosis in human hepatocellular carcinoma cells
Authors: Yuko Takeba
Naoki Matsumoto
Minoru Watanabe
Sachiko Takenoshita-Nakaya
Yuki Ohta
Toshio Kumai
Masayuki Takagi
Satoshi Koizumi
Takeshi Asakura
Takehito Otsubo
Publication date: 01-06-2012
Publisher: Springer-Verlag
Published in: Cancer Chemotherapy and Pharmacology / Issue 6/2012
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-012-1862-6

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Abstract

Purpose

Methods

Results

Conclusion

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