GOTTARDO MarÍa Florencia
congresos y reuniones científicas
PRECLINICAL EFFICACY OF CIGB-300, AN ANTI-CK2 PEPTIDE, ON BREAST CANCER METASTASIC COLONIZATION
GOTTARDO, MARÍA FLORENCIA; SIDABRA, JOHANNA ELENA; CAPOBIANCO, CARLA SABRINA; GARONA, JUAN; PEREA, SILVIO E.; ALONSO, DANIEL; FARINA, HERNAN GABRIEL
Congreso; AACR ANNUAL MEETING 2020; 2020
CK2 is a serine/threonine kinase that is overexpressed in breast cancer and its inhibition is associated to reduced tumor growth and disease progression. With more than three hundred substrates, this kinase is involved in a large number of cellular functions, such as replication, cell proliferation, differentiation, regulation of apoptosis and angiogenesis. CIGB-300 is an antitumor peptide with a novel mechanism of action, since it binds to the phospho-acceptor domain of CK2 substrates impairing the correct phosphorylation by the enzyme. Our aim was to evaluate the potential therapeutic benefits of CIGB-300 on breast cancer disease using experimental models with translational relevance. We demonstrated that CIGB-300 reduces breast cancer cell growth in MDA-MB-231, MCF-7 and F3II cells, exerting a pro-apoptotic action. We found that CIGB-300 increased Bax and decreased Bcl-2 expression, so the intrinsic pathway was involved in the proapoptotic effect of CIGB-300 in breast cancer cells. Moreover, CIGB-300 inhibits the CK2-mediated phosphorylation of B23, such phosphorylation impairment was correlated with the ability of CIGB-300 to induce nucleolar disassembly. Also, we investigate whether CIGB-300 affects the sensitivity of tumor cells to chemotherapeutic agents. We evaluated the effects of the combination of CIGB-300 and cisplatin on cell viability and apoptosis. We demonstrated that CIGB-300 sensitize breast cancer cells to cisplatin, reducing cell viability and increasing apoptosis. In vivo, the effect on experimental breast cancer lung metastasis was evaluated after surgical removal of primary F3II tumors or after tail vein injection of tumor cells. Systemic CIGB-300 treatment inhibited breast cancer colonization of the lung, reducing the size and number of metastatic lesions. The present preclinical study establishes for the first time the efficacy of CIGB-300 on breast cancer. These encouraging results suggest that CIGB-300 could be used for the management of breast cancer as an adjuvant therapy after surgery, limiting tumor metastatic spread and thus protecting the patient from distant recurrence.