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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  ;  Do Young Kim  ;  Da Young Kim  ;  Kyung-Ju Cho  ;  Jeon Han Park  ;  Ho Yeong Lim  ;  Kwang-Hyub Han 
Citation
 Cancer Chemotherapy and Pharmacology, Vol.76(2) : 257-267, 2015 
Journal Title
 Cancer Chemotherapy and Pharmacology 
ISSN
 0344-5704 
Issue Date
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
https://ir.ymlib.yonsei.ac.kr/handle/22282913/140705
DOI
10.1007/s00280-015-2787-7
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
1. Journal Papers (연구논문) > 5. Research Institutes (연구소) > Institute of Gastroenterology (소화기병연구소)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실)
Yonsei Authors
김도영(Kim, Do Young)
노원상(Ro, Simon Weonsang)
박전한(Park, Jeon Han)
한광협(Han, Kwang Hyup)
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Full Text
http://link.springer.com/article/10.1007%2Fs00280-015-2787-7
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