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

VERA MARINA C.; LUCCI, ALVARO; LORENZETTI, FLORENCIA; COMANZO, CARLA G.; HEIT BARBINI, FRANCISCO J.; FERRETTI, ANABELA C.; CEBALLOS, MARÍA P.; ALVAREZ, MARÍA DE LUJÁN; QUIROGA, ARIEL D.; CARRILLO, MARÍA C.

Rosario

Congreso; Reunión anual SAFIS 2019 ROSARIO; 2019

safis

IFN-α is the primary choice for viral hepatitis treatmentand a promising therapy for hepatocellular carcinoma(HCC). Vitamin K2 (VK2) exerts growth-inhibitory effects inseveral human cancer cells, including HCC. We previouslyreported that VK2 blocks the beneficial effects ofinterferon alpha 2b (IFN-α-2b) administered on the earlystages of liver cancer development in rats. However, littleis known on the mechanism. Objective: to further evaluatethe effects of IFN-α-2b and VK2 in a human hepatic cancercell line. Methods and Results: We used the human livercancer cell line SK-Hep 1. The cells were treated with10000 U/I of IFN-α-2b, 25 µM of VK2. Treatments wereperformed alone (IFN-group, VK2-group) or combined(IFN-VK2-group). The length of each treatment variedaccording to the experiment to be carried out. Weperformed the MTT assay to determine cell viability 24hours after treatment, the wound healing assay todetermine migration was performed 20 hours aftertreatment, and the invasion test in transwell chamberswas performed 48 hours after initiation of treatments. Nochanges in cell viability were found with any of thetreatments. On the other hand, IFN-treated cells showeda decrease (-15 %*) on migration, whereas VK2 and IFNVK2 groups did not show any differences respect tocontrol group. In line, IFN-group showed a significantdiminution (-25%*) on invasion and VK2 treatmentblocked the effect of IFN in the combined group. VK2 alonehad no effects in this assay. Conclusion: there is nobeneficial effect in treating human liver cancer cells withVK2. Moreover, VK2 blocks the positive effects of IFN-α-2bin cell migration and invasion. This is in agreement withour in vivo studies and seems to be clear that VK2interferes with the beneficial cellular actions exerted byIFN-α-2b, ultimately leading to undesired final outcomes