Evaluating the Anticancer Activity of Blocking TNF Type 1 Receptors in Thioacetamide-Induced Hepatocellular Carcinoma in a Rat Model.

Abstract

Background Hepatocellular carcinoma (HCC) can explicate about 90% of the total primary liver cancer cases, with approximately 800,000 new cases identified each year worldwide. In addition, any changes in the expression of the tumor necrosis factor α (TNF-α) type 1 receptor (TNFR1) might impact many biological processes, which may lead to cancer. Aims We conducted the following study to investigate the ability of CAY10500, a TNF-α inhibitor that prevents binding to the TNF receptor 1, to produce anticancer effects against hepatocellular carcinoma experimentally induced in rats and to discover its effect on nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Materials and methods HCC was induced in rats via 200 mg/kg thioacetamide followed by treating some rats with IV 1 mg/kg CAY10500. Assessment of the liver impairment was by measuring the serum α-fetoprotein (AFP) and investigation of liver sections stained with hematoxylin/eosin. The hepatic expression of both the messenger RNA (mRNA) and protein levels ofTNF-α, TNFR1, Nrf2, and HO-1 was assessed. Results We found that CAY10500 increased the survival percent of rats associated with a reduction in serum AFP and the number of hepatic nodules. Besides, CAY10500 reduced the expression of TNFR1 without affecting the expression of TNF-α. Finally, CAY10500 increased the expression of both Nrf2 and HO-1. Conclusions Inhibition of TNFR1 expression in HCC by using CAY10500 produced therapeutic effects as indicated by increasing the survival rate, reducing the serum AFP level, decreasing liver nodules, and improving hepatocytes' structure. In addition, TNFR1 significantly enhanced the expression of Nrf2 and HO-1.