Effects of interferon alpha 2b (IFN‐α2B) combined with vitamin k2 (VK2) on altered hepatic foci (AHF) in rats

VERA, MC; LORENZETTI, F; LUCCI, A; COMANZO, CG; FERRETTI, A; CEBALLOS, MP; ALVAREZ ML; QUIROGA, AD; CARRILLO, MC

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

IFN-α is the primary choice for viral hepatitis treatment and apromising therapy for hepatocellular carcinoma (HCC). VK2 exertsgrowth-inhibitory effects in several human cancer cells, includingHCC. Objective: to evaluate if the combined therapy of IFN-α2bwith VK2 has a synergistic inhibitory action on the development ofliver cancer, cell proliferation, apoptosis and fibrosis. Methods andResults: Adult male Wistar rats were subjected to a 2-phase modelof liver cancer. Rats received 2 ip doses of diethylnitrosamine (150mg/kg) 2 weeks apart and, one week after, they received 20 mg/kg of 2-acetylaminofluorene by gavage 3 days/week for 3 weeks(IP group). Animals were divided into 4 groups: IP; IFN: IP rats thatreceived IFN-α2b 6.5x105 U/kg ip 3 times/week/3 weeks; VK2: IPrats that received VK2 8 mg/kg ip 3 times/week/3 weeks; and IFN+-VK2: IP rats which received both drugs. Animals were euthanizedafter treatments and livers were obtained. AHF were determinedby immunohistochemistry using anti rGST-P and number of AHF/liver and % AHF/liver were calculated. As expected IP rats showeda decrease in number (-39%*) and % (-65 %*) of AHF/liver uponIFN treatment. VK2 and IFN+VK2 groups did not show differencesrespect to IP. Analysis of liver fibrosis (Direct Red 80/picric acidstaining) showed a reduction in IFN and IFN+VK2 groups (-32%* and -31%*, respectively). Immunoblot analysis showed an increasein mitochondrial proapoptotic Bax protein in IFN and IFN+VK2groups (+219%* and +97%* respectively), and in antiapoptotic Bcl-2(+94%*) in VK2 group. In addition, Bax/Bcl-2 ratios were calculated,IP: 1, IFN: 3.2±0.2*, VK2:0.5±0.1, IFN+VK2:1.4±0.07 (*p