Animal models as a tool in hepatocellular carcinoma research: A Review

Abstract

Cancer is the first cause of death in developed countries and the second in developing countries. Concerning the most frequent worldwide-diagnosed cancer, primary liver cancer represents approximately 4% of all new cancer cases diagnosed globally. However, among primary liver cancer, hepatocellular carcinoma is by far the most common histological subtype. Notwithstanding the health promotion and disease prevention campaigns, more than half a million new hepatocellular carcinoma cases are reported yearly, being estimated to growth continuously until 2020. Taking this scenario under consideration and the fact that some aspects concerning hepatocellular carcinoma evolution and metastasize process are still unknown, animal models assume a crucial role to understand this disease. The animal models have also provided the opportunity to screen new therapeutic strategies. The present review was supported on research and review papers aiming the complexity and often neglected chemically induced animal models in hepatocarcinogenesis research. Despite the ongoing debate, chemically induced animal models, namely, mice and rat, can provide unique valuable information on the biotransformation mechanisms against xenobiotics and apprehend the deleterious effects on DNA and cell proteins leading to carcinogenic development. In addition, taking under consideration that no model achieves all hepatocellular carcinoma research purposes, criteria to define the "ideal" animal model, depending on the researchers' approach, are also discussed in this review.

Effects of Wnt‑1 blockade in DEN‑induced hepatocellular adenomas of mice

“…The relatively low proliferating index, which is a typical feature of human hepatocellular adenoma as well (30), probably reflects the low proliferation rate of hepatocytes that in normal conditions rest in the G 0 phase of the cell cycle. It also explains the slow growth of hepatocellular tumors in DEN-treated rodent models, that, as in the present study, are not further manipulated to promote tumor initiation and growth (1,2). Similarly to proliferation, apoptosis in hepatocellular adenomas of mice has also been reported to be as low as 0.02 to 0.44% regardless of mouse strain and induction of carcinogenesis protocol (29,(31)(32)(33).…”

“…Rodent models of HCC have been proven useful in revealing aspects of its multistep pathogenesis and preclinical testing of anti-HCC treatments (1,2). Mice have been shown to be particularly useful in that regard and a wide variety of genetically engineered, xenograft and chemically induced models are available for HCC research (1,2,4,5).…”

“…Among them, the chemically induced model that utilizes diethylnitrosamine (DEN) for HCC initiation is widely used and well-characterized. This model recapitulates aspects of liver injury and fibrosis and hepatitis, which both are the basis of human HCC (1,2,4,6). For that, and because it is comparable to its human counterpart in terms of cancer-associated gene expression patterns and carcinogenetic pathways, it is considered among the best-fit experimental models of HCC (5).…”

“…Hepatocellular carcinoma (HCC) is the most common type of liver cancer and among leading causes of cancer-related death of humans (1)(2)(3). Rodent models of HCC have been proven useful in revealing aspects of its multistep pathogenesis and preclinical testing of anti-HCC treatments (1,2).…”

Hinokitiol-Ameliorated Diethylnitrosamine-Induced Hepatocarcinogenesis Through Antioxidant Mechanism in Rats: In Vitro and in Vivo Study

“…Many of the research works were carried out by the researchers all over world to assess the potent therapeutic compound from medicinal plants for various diseases including tumor. Cancer is the one of the complicated diseases receiving the great interest to resolve in present scenario [25,26].…”