Please use this identifier to cite or link to this item: https://doi.org/10.1007/s00109-013-1095-0
Title: Simvastatin sensitizes human gastric cancer xenograft in nude mice to capecitabine by suppressing nuclear factor-kappa B-regulated gene products
Authors: Manu, K.A.
Shanmugam, M.K. 
Li, F.
Chen, L.
Siveen, K.S.
Ahn, K.S.
Kumar, A.P. 
Sethi, G.
Keywords: Apoptosis
Chemoresistance
Gastric cancer
NF-κB
Simvastatin
Issue Date: 2014
Citation: Manu, K.A., Shanmugam, M.K., Li, F., Chen, L., Siveen, K.S., Ahn, K.S., Kumar, A.P., Sethi, G. (2014). Simvastatin sensitizes human gastric cancer xenograft in nude mice to capecitabine by suppressing nuclear factor-kappa B-regulated gene products. Journal of Molecular Medicine 92 (3) : 267-276. ScholarBank@NUS Repository. https://doi.org/10.1007/s00109-013-1095-0
Abstract: Chemoresistance remains a major problem in the treatment of gastric cancer patients. Hence, novel pharmacological agents that can overcome drug resistance are urgently required. Whether simvastatin can sensitize the gastric cancer to the antitumor effects of capecitabine in vitro and in vivo was investigated. The effect of simvastatin on the proliferation of gastric cancer cells was examined by mitochondrial dye-uptake 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide method, apoptosis by esterase staining, NF-κB activation by DNA binding assay, and protein expression by western blot analysis. The effect of simvastatin on the tumor growth in xenograft mouse model of human gastric cancer was also examined. Simvastatin suppressed the proliferation of gastric cancer cells, enhanced the apoptotic effects of capecitabine, suppressed the constitutive activation of NF-κB, and abrogated the expression of cyclooxygenase-2 (COX-2), cyclin D1, Bcl-2, survivin, CXC motif receptor 4, and MMP-9 proteins. In a xenograft mouse model, we observed that the administration of simvastatin alone (5 mg/kg body weight, intraperitoneal thrice/week) significantly suppressed the growth of the tumor and this effect was further potentiated by capecitabine treatment. As compared to the vehicle control, simvastatin also suppressed the expression of NF-κB-regulated gene products such as cyclin D1, COX-2, ICAM-1, MMP-9, survivin, Bcl-xL, and XIAP in tumor tissues. Overall, our results demonstrate that simvastatin can enhance the effects of capecitabine through suppression of NF-κB-regulated markers of proliferation, invasion, angiogenesis, and metastasis. Key message: Simvastatin suppressed the proliferation and augmented apoptotic effects of capecitabine. Simvastatin suppressed constitutive activation of NF-κB and its regulated genes. Simvastatin enhanced the tumor growth inhibitory effects of capecitabine. © 2013 Springer-Verlag Berlin Heidelberg.
Source Title: Journal of Molecular Medicine
URI: http://scholarbank.nus.edu.sg/handle/10635/109653
ISSN: 14321440
DOI: 10.1007/s00109-013-1095-0
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

123
checked on Dec 5, 2022

WEB OF SCIENCETM
Citations

116
checked on Nov 28, 2022

Page view(s)

125
checked on Nov 24, 2022

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.