Study of the effects of cyclooxygenase-2 inhibitor on the promotion of hepatic tumorigenesis in rats fed a high fat diet.
OBJECTIVE
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The highest prevalence of hepatitis is an important risk factor contributing to development of HCCs. However, an increasing number of cases are associated metabolic disease and steatohepatitis. Inflammation associated with many liver disease, seems to be a necessary pre-requisite for successful tumor initiation. Mechanisms that link high fat diet and inflammation initial stage of HCC are not completely understood. The present work was designed to investigate the effect of fat, through modulation of the insulin-like growth factors I and II (IGF-I and IGF-II), on the promotion of hepatocellular carcinoma, and the role of cyclooxygenase 2 (COX-2).


METHODS
two main groups of rats were used: control and HCC groups. The HCC group was further sub-divide in to two subgroups, HCC fed with standard diet and HCC fed with high fat diet. The effects of celecoxib were also investigated in HCC fed with high fat diet.


RESULTS
We found that high fat diet was associated with significant increases in COX2 and interleukin 6 (IL6) with significant promotion of HCC progression. The significant increase in IGF could contribute partially to the observed effects of high fat diet. In addition, celecoxib was found to significantly reduce HCC progression.


CONCLUSIONS
We conclude that COX2 could play central role in high prevalence of HCC observed with high fat diet. Several triggering factors such as IGF and IL6, together with the direct modulation of fat metabolism could open several novel preventive strategies of celecoxib treatment, and could be useful biomarkers for assessment of its pharmacological effects.
Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Magda
M
Hamzawy
Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Laila
L
Elsaid
Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Asmaa
A
Shams
Department of Biochemistry, Faculty of Medicine, Cairo University, Cairo, Egypt.
Laila
L
Rashid
Department of Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Soheir
S
Mahfouz
Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Nivin
N
Sharawy
AFP, alpha-fetoprotein; CCl4, carbon-tetrachloride; COX-2, cyclooxygenase 2; FAS, fatty acid synthase; FFA, free fatty acid; GH, growth hormone; H&E, Hematoxylin and Eosin stain; HCC, hepatocellular carcinoma; IGF; IGF-I and IGF-II, insulin-like growth factors I and II; IGFBP-3, insulin-like growth factor-binding protein 3; IGFR, IGF receptor; IL6, interleukin 6; IκB, inhibitory protein; JNK1, c-Jun N-terminal kinase-1; MAPK, mitogen-activated protein kinase; NFκB, nuclear factor-κB; PAS, periodic acid Schiff stain; PI3k, phosphatidylinositide 3-kinases; TAG, triaceyl glycerol; celecoxib; fat diet; hepatocellular carcinoma; real time-PCR, real time-polymerase chain reaction