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Cited 13 time in webofscience Cited 13 time in scopus
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Synergistic effect of simvastatin plus NS398 on inhibition of proliferation and survival in hepatocellular carcinoma cell line

Authors
Lee, Sun JaeHwang, Ji WonYim, HyungshinYim, Hyung JoonWoo, Sang UkSuh, Sang JunHyun, Jong JinJung, Sung WooKoo, Ja SeolKim, Ji HoonSeo, Yeon SeokYeon, Jong EunLee, Sang WooByun, Kwan SooUm, Soon Ho
Issue Date
Jun-2014
Publisher
Blackwell Publishing Inc.
Keywords
combination drug therapy; hepatocellular carcinoma; cyclooxygenase-2 inhibitor; simvastatin
Citation
Journal of Gastroenterology and Hepatology, v.29, no.6, pp 1299 - 1307
Pages
9
Indexed
SCI
SCIE
SCOPUS
Journal Title
Journal of Gastroenterology and Hepatology
Volume
29
Number
6
Start Page
1299
End Page
1307
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/9258
DOI
10.1111/jgh.12503
ISSN
0815-9319
1440-1746
Abstract
Background and Aims NS398, a selective cyclooxygenase-2 inhibitor, and simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, both exert an anticancer effect on hepatocellular carcinoma cells, but the effect of co-administration of the two drugs remains unknown. We aimed to investigate the synergistic in vitro anticancer effect of co-administration of NS398 and simvastatin and its mechanism. Methods The Hep3B and Huh-7 cell lines were cultured. Cells were treated with simvastatin, NS398, or a combination. 5-bromo-2′-deoxyuridine ELISA assay, flow cytometry, Western blot analyses, and immunofluorescence assay were performed. Results In both cell lines, co-administration of simvastatin and NS398 resulted in a greater effect on proliferation and apoptosis. In Hep3B cells, co-administration of the two drugs resulted in a greater decrease in procaspase 3 and Bcl-2 and an increase in cleaved caspase 9 than that noted with monotherapy. In Huh-7 cells, co-administration of the two drugs resulted in a greater decrease in procaspase 3 and cyclin D1 and an increase in cleaved caspase 9. Expression of NF-κB and Akt were also decreased to a greater extent when the two drugs were co-administered in both cell lines. Immunofluorescence assay showed suppression of the nuclear localization of NF-κB by simvastatin or NS398. The effect was greater by co-administration. Conclusions The co-administration of NS398 and simvastatin produced greater antiproliferative and proapoptotic effects against Hep3B cells and Huh-7 cells. Inhibition of the NF-κB and Akt pathway and activation of caspase cascade, which are considered as the major mechanism of synergistic anticancer properties, were observed in both cell lines.
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Kim, Ji Hoon
Guro Hospital (Department of Gastroenterology and Hepatology, Guro Hospital)
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