Synergistic Effect of Caloric Restriction and Cyclooxygenase-2 Inhibitor “Celecoxib” Against IGFs/COX-2 Mediating Chemically Induced Hepatocellular Carcinoma in Rats

Caloric restriction (CR) alongside its ability to increase longevity, exerts inhibitory effects against various tumors.The purpose of this current research was to investigate the conceivable implications of CR, either independently or in conjunction with a cyclooxygenase 2 inhibitor (Celecoxib), on the pathophysiology of induced hepatocellular carcinoma (HCC).Forty adult male Wistar rats were allocated into four groups: Control, HCC; induced by injecting diethylnitrosamine intraperitoneally, then subsequently given a weekly subcutaneous injection of carbon tetrachloride (CCl4) once a week for 6 consecutive weeks, CR group, and CR-Celecoxib group.The results revealed enhanced serum insulin growth factor-I (IGF-I) and-II (IGF-II) levels, along with a significant increase in COX-2 and IL-6 gene expression as well as acceleration of pathological changes, glycogen depletion, enhanced fibrosis, and decreased caspase 3 expression in the liver.However, both IGF-I, II, and alpha-fetoprotein (AFP) were significantly decreased in the CR group co-treated with Celecoxib which was positively reflected on the liver architecture.We concluded that combined CR and COX-2 inhibition interferes with the pathogenesis of HCC.