RESEARCH OF ANTINEOPLASTIC ACTIVITY OF CHIMERIC PEPTIDE P16_ANTP IN VIVO

T.M. Kulinich, A.N. Boldyrev, V.K. Bozhenko
Russian Scientific Center of Reontgen Radiology, Profsoyuznaya Str., 86, Moscow, Russian Federation, 117997

Introduction. P16INK4a protein plays one of the key role in processes of cell proliferation, its inactivation is noted in a number of tumors of various localization. Restoration of the p16INK4a function in neoplastic cells may promote braking of division of tumor cells and their elimination. The search of artificially synthesized, functionally active, short fragments of protein р16 and methods fot their intracellular delivery is an actual problem of modern tumor target therapy. The aim of the study. In vivo research of antineoplastic activity of the sequence 82-102 from P16INK4a protein as a part of the chimeric peptide, which includes the sequence of ANTP as a vector for intracellular delivery. Methods. Antitumor effect in vivo was investigated on xenograft models of HCT116, A-549 (concentration p16_ANTP – 5 mg/kg, using a thrice weekly dosing schedule). 40 mice females of Balb/c nude, at the age of 8 weeks, with a body weight of 20-22 g were used. The volume of tumors was calculated according to the product of values of 3 mutually perpendicular diameters of nodes. Results. Intratumoral introduction of chimeric p16_ANTP peptide leads to the reliable growth inhibition on experimental human tumor models – colorectal cancer (HCT-116) and lung carcinoma (A549) by 66,8% and 58,7% accordingly. Conclusion. The chimeric p16_ANTP peptide which includes functional part – 82-102 fragment of p16INK4A and an internalizing vector of Antennapedia, possesses the expressed antineoplastic activity.
Keywords: 
p16INK4a, inhibitors cyclin of kinases, cell penetrating peptides (CPP), antitumor target therapy