Preclinical efficacy of CIGB-300, an anti-CK2 peptide, on breast cancer metastasic colonization

被引:13
作者
Gottardo, Maria F. [1 ]
Capobianco, Carla S. [1 ]
Sidabra, Johanna E. [1 ]
Garona, Juan [1 ]
Perera, Yasser [2 ]
Perea, Silvio E. [2 ]
Alonso, Daniel F. [1 ]
Farina, Hernan G. [1 ]
机构
[1] Natl Univ Quilmes, Dept Sci & Technol, Lab Mol Oncol, Roque Saenz Pena 352,B1876BXD Bernal, Buenos Aires, DF, Argentina
[2] Ctr Genet Engn & Biotechnol CIGB, Div Pharmaceut, Lab Mol Oncol, Havana, Cuba
关键词
PROTEIN-KINASE CK2; PROAPOPTOTIC PEPTIDE; CK2-MEDIATED PHOSPHORYLATION; INHIBITS ANGIOGENESIS; LUNG METASTASIS; TUMOR-GROWTH; IN-VITRO; IMPAIRS; APOPTOSIS; OUTCOMES;
D O I
10.1038/s41598-020-71854-6
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
CK2 is a serine/threonine kinase that is overexpressed in breast cancer and its inhibition is associated to reduced tumor growth and disease progression. CIGB-300 is an antitumor peptide with a novel mechanism of action, since it binds to protein kinase CK2 catalytic subunit alpha and to CK2 substrates thus preventing the enzyme activity. 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 and cell cycle arrest. We also found that CIGB-300 decreased cell adhesion, migration and clonogenic capacity of malignant cells. Effect on experimental breast cancer lung metastasis was evaluated after surgical removal of primary F3II tumors or after tail vein injection of tumor cells, also we evaluated CIGB-300 effect on spontaneous lung metastasis in an orthotopic model. 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.
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页数:11
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