Vitamin K2 blocks the inhibitory effects of interferon alpha 2b on migration and invasion of liver cancer cells.

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

Congreso; SAFIS; 2019

IFN-α is the primary choice for viral hepatitis treatment and a promising therapy for hepatocellular carcinoma (HCC). Vitamin K2 (VK2) exerts growth-inhibitory effects in several human cancer cells, including HCC. We previously reported that VK2 blocks the beneficial effects of interferon alpha 2b (IFN-α-2b) administered on the early stages of liver cancer development in rats. However, little is known on the mechanism. Objective: to further evaluate the effects of IFN-α-2b and VK2 in a human hepatic cancer cell line. Methods and Results: We used the human liver cancer cell line SK-Hep 1. The cells were treated with 10000 U/I of IFN-α-2b, 25 μM of VK2. Treatments were performed alone (IFN-group, VK2-group) or combined (IFN-VK2-group). The length of each treatment varied according to the experiment to be carried out. We performed the MTT assay to determine cell viability 24 hours after treatment, the wound healing assay to determine migration was performed 20 hours after treatment, and the invasion test in transwell chambers was performed 48 hours after initiation of treatments. No changes in cell viability were found with any of the treatments. On the other hand, IFN-treated cells showed a decrease (-15 %*) on migration, whereas VK2 and IFN-VK2 groups did not show any differences respect to control group. In line, IFN-group showed a significant diminution (-25%*) on invasion and VK2 treatment blocked the effect of IFN in the combined group. VK2 alone had no effects in this assay. Conclusion: there is no beneficial effect in treating human liver cancer cells with VK2. Moreover, VK2 blocks the positive effects of IFN-α-2b in cell migration and invasion. This is in agreement with our in vivo studies and seems to be clear that VK2 interferes with the beneficial cellular actions exerted by IFN-α-2b, ultimately leading to undesired final outcomes.