CIGB-300, an anti-CK2 peptide, inhibits angiogenesis, tumor cell invasion and metastasis in lung cancer models.

BENAVENT F; CAPOBIANCO CS; GARONA J; CIRIGLIANO SM; PERERA Y; URTREGER AJ; PEREA SE; ALONSO DF; FARINA HG

LUNG CANCER

ELSEVIER IRELAND LTD

Lugar: Amsterdam; Año: 2016 p. 14 - 21

0169-5002

Casein kinase 2 (CK2) is overexpressed in several types of cancer. It has more than 300 sub-strates mainly involved in DNA reparation and replication, chromatin remodeling and cellular growth. Inrecent years CK2 became an interesting target for anticancer drug development. CIGB-300 is a peptidicinhibitor of CK2 activity, designed to bind to the phospho-acceptor domain of CK2 substrates, impairingthe correct phosphorylation by the enzyme. The aim of this work was to explore the antitumor effects ofthis inhibitor in preclinical lung cancer models.Materials and methods: Human H125 and murine 3LL Lewis lung carcinoma cell lines were used to evaluatethe effect of CIGB-300 treatment in vitro. For this purpose, adhesion, migration and invasion capabilitiesof cancer cells were tested. Proteolytic activity of tumor cell-secreted uPA and MMP after CIGB-300incubation was also analyzed.In vivo anticancer efficacy of the peptide was evaluated using experimental and spontaneous lungcolonization assays in C57BL/6 mice. Finally, in order to test the effect of CIGB-300 on tumor cell-inducedangiogenesis, a modified Matrigel plug assay was conducted.Results and conclusion: We demonstrate that treatment with low micromolar concentrations of CIGB-300caused a drastic reduction of adhesion, migration and invasion of lung cancer cells. Reduced invasivenessafter CIGB-300 incubation was associated with decreased proteolytic activity of tumor cell-conditionedmedium.In vivo, intravenous administration of CIGB-300 (10 mg/kg) markly decreased lung colonization andmetastasis development of 3LL cells. Interestingly, after 5 days of systemic treatment with CIGB-300,tumor cell-driven neovascularization was significantly reduced in comparison to control group. Alto-gether our data suggest an important role of CK2 in lung tumor development, suggesting a potential useof CIGB-300 as a novel therapeutic agent against lung cancer.