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2017 ; 8
(35
): 58353-58363
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Preventive effects of the sodium glucose cotransporter 2 inhibitor tofogliflozin
on diethylnitrosamine-induced liver tumorigenesis in obese and diabetic mice
#MMPMID28938561
Obara K
; Shirakami Y
; Maruta A
; Ideta T
; Miyazaki T
; Kochi T
; Sakai H
; Tanaka T
; Seishima M
; Shimizu M
Oncotarget
2017[Aug]; 8
(35
): 58353-58363
PMID28938561
show ga
Sodium glucose cotransporter 2 inhibitors are expected to ameliorate the
abnormalities associated with metabolic syndrome including non-alcoholic fatty
liver disease. In this study, we investigated the effects of the sodium glucose
cotransporter 2 inhibitor tofogliflozin on the development of non-alcoholic fatty
liver disease-related liver tumorigenesis in C57BL/KsJ-+Lepr (db) /+Lepr (db)
obese and diabetic mice. The direct effects of tofogliflozin on human liver
cancer cell proliferation were also evaluated. Mice were administered
diethylnitrosamine-containing water for 2 weeks and were treated with
tofogliflozin throughout the experiment. In mice treated with tofogliflozin, the
development of hepatic preneoplastic lesions was markedly suppressed, and hepatic
steatosis and inflammation significantly reduced, as evaluated using the
non-alcoholic fatty liver disease activity score, in comparison with the control
mice. Serum levels of glucose and free fatty acid and mRNA expression levels of
pro-inflammatory markers in the liver were reduced by tofogliflozin treatment.
Conversely, the proliferation of sodium glucose cotransporter 2
protein-expressing liver cancer cells was not inhibited by this agent. These
findings suggest that tofogliflozin suppressed the early phase of obesity- and
non-alcoholic fatty liver disease-related hepatocarcinogenesis by attenuating
chronic inflammation and hepatic steatosis. Therefore, sodium glucose
cotransporter 2 inhibitors may have a chemopreventive effect on obesity-related
hepatocellular carcinoma.