VITAMIN K2 (VK2) SUPPLEMENTATION BLOCKS THE ANTIAPOPTOTIC EFFECT OF INTERFERON ALPHA 2B (IFN-Α-2B) ON THE EARLY STAGES OF LIVER CANCER DEVELOPMENT IN RATS

LUCCI ALVARO; QUIROGA ARIEL DARÍO; LORENZETTI FLORENCIA; ALVAREZ MARÍA DE LUJÁN; VERA MARINA CECILIA; COMANZO CARLA GABRIELA

Mar del Plata

Congreso; Reunión conjunta SAI SAIC SAFIS 2018; 2018

Sociedad Argentina de Investigación Clínica (SAIC), Sociedad Argentina de Inmunología (SAI), Sociedad Argentina de Fisiología (SAFIS)

VK2 holds anticancer properties. On the other hand, IFN-α-2b inhibits the development of altered (preneoplasic) hepatic foci (AHF) by apoptosis. Objective: to evaluate the effects of IFN-α-2b supplemented with VK2 on the onset of liver cancer development in rats. Methods and Results: Adult male Wistar rats were subjected to a 2-phase model of liver cancer. Rats received 2 ip doses of carcinogenic diethylnitrosamine (150 mg/kg) 2 weeks apart and, one week after, they received 20 mg/kg of the promotor 2-acetylaminofluorene by gavage 3 days/week for 3 weeks (IP group). Animals were divided into 4 groups: IP; IFN: IP rats that received IFN-α2b 6.5x105U/ kg ip 3 times/week/3 weeks; VK2: IP rats that received VK2 8 mg/ kg ip 3 times/week/3 weeks; and IFN+VK2: IP rats which received both drugs. Animals were euthanized after treatments and livers were obtained. Caspase-3 activity in liver lysates was significantly increased in IFN group respect to IP group. VK2 had no effects on caspase-3 activity. Immunoblot analysis of p53 protein in nuclear fractions showed an increase (+75%*) in IFN group compared to IP group, whereas VK2 treatment reduced the levels of the protein (-54%*). Bcl-2 was evaluated by immunohistochemistry. An astonishing staining outside the AHF was observed in the IP group. By contrast, the IFN group presented less stained cells, distributed both inside and outside the AHF. VK2 IFN+VK2 groups presented a pattern similar to IP group, with more Bcl-2-positive cells within the AHF. Immunoblotting and immunohistochemistry showed no differences in the PCNA and cyclin D1 protein expression between all the studied groups. (*p