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Title: Bevacizumab and rapamycin induce growth suppression in mouse models of hepatocellular carcinoma
Authors: Huynh, H. 
Yu, K.
Wu, J.
Lee, M.H.
Hor, H.
Soo, K.C. 
Toh, H.C. 
Tan, P. 
Salto-Tellez, M. 
Chow, P.K.H. 
Lee, C.K.
Soong, R. 
Goh, B.C. 
Lee, H.S. 
Somani, A.
Tan, P.H. 
Palanisamy, N.
Kalpana, R.
Keywords: Angiogenesis
Liver cancer
mTOR inhibition
Issue Date: 2008
Citation: Huynh, H., Yu, K., Wu, J., Lee, M.H., Hor, H., Soo, K.C., Toh, H.C., Tan, P., Salto-Tellez, M., Chow, P.K.H., Lee, C.K., Soong, R., Goh, B.C., Lee, H.S., Somani, A., Tan, P.H., Palanisamy, N., Kalpana, R. (2008). Bevacizumab and rapamycin induce growth suppression in mouse models of hepatocellular carcinoma. Journal of Hepatology 49 (1) : 52-60. ScholarBank@NUS Repository.
Abstract: Background/Aims: Hepatocellular carcinoma is a leading cause of global cancer mortality, with standard chemotherapy being minimally effective in prolonging survival. We investigated if combined targeting of vascular endothelial growth factor protein and expression might affect hepatocellular carcinoma growth and angiogenesis. Methods: We treated patient-derived hepatocellular carcinoma xenografts with (i) bevacizumab; (ii) rapamycin; and (iii) bevacizumab plus rapamycin. Western blotting was employed to determine changes in the proteins. Apoptosis, vascular endothelial growth factor expression, microvessel density, and cell proliferation were analyzed by immunohistochemistry. Results: Hepatocellular carcinoma growth was inhibited by bevacizumab plus rapamycin treatment to a significantly greater degree than bevacizumab or rapamycin monotherapy. Reductions in tumor growth by bevacizumab plus rapamycin were associated with inhibition of downstream targets of the mammalian target-of-rapamycin pathway, reductions in vascular endothelial growth factor expression, and tumor microvessel density. Potentially additive effects of bevacizumab plus rapamycin included reductions in vascular endothelial growth factor expression, cyclin D1, and cyclin B1. In an intra-peritoneal model of hepatocellular carcinoma, bevacizumab plus rapamycin potently inhibited both intra-liver and intra-abdominal tumor growth, reduced ascites levels, and significantly prolonged mouse survival. Conclusions: Bevacizumab and rapamycin, which are both clinically approved drugs, may represent a novel molecularly-targeted combination treatment for hepatocellular carcinoma. © 2008 European Association for the Study of the Liver.
Source Title: Journal of Hepatology
ISSN: 01688278
DOI: 10.1016/j.jhep.2008.02.022
Appears in Collections:Staff Publications

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