The anti-ck2 peptide cigb-300 elicits an antitumor effect in vitro and inhibits metastatic dissemination in vivo in an aggressive murine mammary carcinoma model

CARLA SABRINA CAPOBIANCO; JOHANNA ELENA SIDABRA; YASSER PERERA; SILVIO PEREA; DANIEL FERNANDO ALONSO; HERNAN GABRIEL FARINA

Mar del Plata

Congreso; LXI Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2016

Sociedad Argentina de Investigación Clínica (SAIC).

CK2 is a holoenzyme overexpressed in several types of cancer. It has more than 300 substrates mainly involved in DNA reparation and replication, chromatin remodeling and cellular growth. In recent years CK2 became an interesting target for anticancer drug development. CIGB-300 is a peptidic inhibitor of CK2, designed to bind to the phospho-acceptor domain of CK2 substrates, impairing the correct phosphorylation by the enzyme. Previously, it was demonstrated that CK2 inhibition was able to significantly reduce primary tumor growth using heterotopic cervix and lung cancer models. Both in vitro and in vivo, CIGB-300 also displayed an important anti-angiogenic and pro-apoptotic effect on tumor cells.Taking into account the fact that breast cancer is one of the main tumor types in which CK2 is overexpressed, and the antitumor effects shown in other tumor types, our focus in this work is to study the effect of CK2 inhibition using CIGB-300 as a modulator of key features of breast cancer cell biology. In this regard, a proliferation and a cell adhesion assay was conducted. In addition, the effect of CIGB-300 treatment in the phosphorylation of the proliferative kinase ERK was measured by Western Blot analysis. In vivo, the effect of intravenous administration in tumor cell dissemination to lung and the growth of local recurrences in an incomplete surgery model was studied.As we expected, CIGB-300 reduced the proliferation (IC50=158 μM) and spreading capability of F3II cancer cells, in addition with a decreased level of ERK phosphorylation. In vivo studies using the syngeneic F3II breast cancer model in Balb/c mice showed a decrease in the number of lung metastases in mice treated systemically with CIGB-300 after primary tumor surgery (Mann Whitney test, p