Synergistic inhibitory effect of gemcitabine and angiotensin type-1 receptor blocker, losartan, on murine pancreatic tumor growt

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Oncol Rep. 2009
Aug;22(2):355-60.


Synergistic inhibitory effect of gemcitabine and angiotensin type-1 receptor
blocker, losartan, on murine pancreatic tumor growth via anti-angiogenic
activities.
 
Noguchi
R
, Yoshiji
H
, Ikenaka
Y
, Namisaki
T
, Kitade
M
, Kaji
K
, Yoshii
J
, Yanase
K
, Yamazaki
M
, Tsujimoto
T
, Kawaratani
H
, Fukui
H
.
Third Department of Internal Medicine, Nara Medical
University, Nara 634-8522, Japan.
Pancreatic cancer is one of the leading causes of cancer
death, and represents a challenging chemotherapeutic problem. The crucial role
of angiogenesis in tumor growth has been widely recognized, and several reports
have revealed that the combination treatment of the conventional
chemotherapeutic drugs and anti-angiogenic agents exerted synergistic
anti-cancerous effects. It has been reported that the clinically used
angiotensin type-1 receptor blocker (ARB) exerted potent anti-angiogenic
activity. The aim of our current study was to examine the combination effect of
gemcitabine (GEM), a widely used conventional chemotherapeutic drug against
pancreas cancer, and losartan (Lo), an ARB, on murine pancreatic tumor growth,
especially in conjunction with angiogenesis. When used individually, GEM and Lo
at clinically comparable low doses moderately suppressed pancreatic tumor
development. The combination treatment with GEM and Lo exerted a marked
inhibitory effect as compared with single agent treatments even after the tumor
was fully established. Neovascularization and the expression of the vascular
endothelial growth factor (VEGF), a central angiogenic factor, in the tumor were
both markedly suppressed in a magnitude similar to the inhibitory effects
against the tumor growth. Since both agents are widely used in the clinical
practice, the combination regimen of GEM and Lo may represent a potential new
therapeutic strategy for pancreatic cancer in the future.