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Efficacy of perifosine alone and in combination with sorafenib in an HrasG12V plus shp53 transgenic mouse model of hepatocellular carcinoma

Title
Efficacy of perifosine alone and in combination with sorafenib in an HrasG12V plus shp53 transgenic mouse model of hepatocellular carcinoma
Authors
Mi Na Kim;Simon Weonsang Ro;Kwang-Hyub Han;Ho Yeong Lim;Jeon Han Park;Kyung-Ju Cho;Da Young Kim;Do Young Kim
Issue Date
2015
Journal Title
Cancer Chemotherapy and Pharmacology
ISSN
0344-5704
Citation
Cancer Chemotherapy and Pharmacology, Vol.76(2) : 257~267, 2015
Abstract
PURPOSE: Perifosine has shown antitumor activity via inhibition of Akt phosphorylation in many advanced solid tumors. This study investigated the efficacy of perifosine alone and in combination with sorafenib in a transgenic mouse model of HCC. METHODS: The mouse model of HCC was generated by hydrodynamic injection of transposons encoding HrasG12V and short-hairpin RNA downregulating p53. The transgenic mice were treated with perifosine alone and in combination with sorafenib to evaluate efficacy of drugs on tumor growth and survival. RESULTS: Treatment with perifosine for 5 weeks, alone and in combination with sorafenib, strongly inhibited tumor growth and increased survival. Perifosine inhibited HCC cell proliferation, induced apoptosis, and decreased tumor angiogenesis. Furthermore, its combination with sorafenib enhanced these effects. In addition, Akt phosphorylation was decreased by perifosine and further decreased by combination treatment. Although perifosine alone did not appear to activate the caspase pathway, combination treatment increased the cleavage of caspase-3, caspase-9, and poly (ADP-ribose) polymerase. CONCLUSIONS: The preclinical effect that current study showed represents a strong rationale for clinical trials using perifosine alone and in combination with sorafenib in the treatment of HCC patients.
URI
http://link.springer.com/article/10.1007%2Fs00280-015-2787-7

http://ir.ymlib.yonsei.ac.kr/handle/22282913/140705
DOI
10.1007/s00280-015-2787-7
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Internal Medicine
1. 연구논문 > 5. Research Institutes > Institute of Gastroenterology
1. 연구논문 > 1. College of Medicine > Dept. of Microbiology
Yonsei Authors
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