Synergistic effect of simvastatin plus NS398 on inhibition of proliferation and survival in hepatocellular carcinoma cell line
- Authors
- Lee, Sun Jae; Hwang, Ji Won; Yim, Hyungshin; Yim, Hyung Joon; Woo, Sang Uk; Suh, Sang Jun; Hyun, Jong Jin; Jung, Sung Woo; Koo, Ja Seol; Kim, Ji Hoon; Seo, Yeon Seok; Yeon, Jong Eun; Lee, Sang Woo; Byun, Kwan Soo; Um, Soon Ho
- Issue Date
- 6월-2014
- Publisher
- WILEY
- Keywords
- combination drug therapy; hepatocellular carcinoma; cyclooxygenase-2 inhibitor; simvastatin
- Citation
- JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, v.29, no.6, pp.1299 - 1307
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
- Volume
- 29
- Number
- 6
- Start Page
- 1299
- End Page
- 1307
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/98292
- DOI
- 10.1111/jgh.12503
- ISSN
- 0815-9319
- Abstract
- Background and AimsNS398, 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. MethodsThe 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. ResultsIn 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-B 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-B by simvastatin or NS398. The effect was greater by co-administration. ConclusionsThe co-administration of NS398 and simvastatin produced greater antiproliferative and proapoptotic effects against Hep3B cells and Huh-7 cells. Inhibition of the NF-B 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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