Therapeutic dose characteristics of the chimeric peptide of MM-D37K at parenteral introduction to the Balb/с nude mice with human colorectal carcinoma HCT-116

Introduction. Within constructed of molecules with a pathogenetic orientation to a tumor cell a row the chimeric of the peptides including the functional fragment with the amino-acid sequence from the SEQ ID NO group is created: 1 - SEQ ID NO: 17 and transport sequence. These peptides are capable at target delivery in the cells to find short functional domains in proteins regulators of various functions. Among them there is MM-D37K blocking G1 phase and inducing an apoptosis in the human tumor cells, including a colorectal cancer HCT-116. It is considered as the potential antineoplastic agent with the corresponding stages of studying. Aim. The aim of the study was an investigation of the MM-D37K dose characteristics at the parenteral administration on the human subcutaneous (s. c.) colorectal cancer xenografts HCT-116. Research problems. 1. Studying of the efficacy of MM-D37K in the dose range at multiple parenteral administration to the Balb/c nude mice with HCT-116. 2. Tolerance control of MM-D37K at multiple parenteral administration to the Balb/c nude mice with HCT-116. Materials and methods. Researches of a chimeric peptide MM-D37K (an inhibitor the cyclin-dependent protein kinases 4/6) are conducted on hypodermic s. c. colorectal cancer xenografts HCT-116 at immunodeficient Balb/c nude mice when using reference criteria assessment of efficacy and tolerance under adequate statistical processing of the results with use of nonparametric Mann-Whitney U-test. Results. It is shown that MM-D37K in single doses of 5 or 10 mg/kg at s. c. or intravenous (i. v.) 5-fold administration in 48 h (total doses 25 or 50 mg/kg) significantly and authentically inhibits the tumor growth within 9 days after the treatment on the level of T/C = 27-43 % (p <0.05) (reference criterion of T/C <42 %) at a well tolerance. At both routes of administration was observed the dose dependence foe efficacy as on T/C and on the maximal effect achievement. There was revealed big deviation of the tumor after the individual sensitivity to a peptide (variability of the tumor size at a larger dose by the i. v administration). Conclusion. The obtained data confirm the sufficient therapeutic range of a MM-D37K chimeric peptide in vivo on the model of a human colorectal cancer HCT-116 allowing to obtained significant reliable anticancer effect at parenteral multiple administrations in the double range of therapeutically doses.

химерный пептид MM-D37K, колоректальный рак человека, мыши Balb/c nude, эффективность, переносимость, chimeric peptide MM-D37K, human colorectal cancer, mice Balb/c nude, efficacy, tolerance

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