ANTITUMOR ACTIVITY OF ANTI-INTEGRIN PROTEIN SAV-RGD ON XENOGRAFTED HUMAN SKIN MELANOMA WITH INTEGRIN AVG3 EXPRESSION

Abstract

Anti-integrins are considered as potential anticancer agents capable of inhibiting differentiation and proliferation of various malignant cells, including disseminated melanoma. The possibility of including anti-integrins with different RGD-motives in combined therapy schedules is discussed. We have studied the oridinal recombinant lyophilized protein SAV-RGD (lyo-SAV-RGD), specifically binding to melanoma cells by means of the Tripeptide Arg-Gly-Asp. As models of melanoma of the skin selected amalonaticus MeWo/mel- and pigmented melCher/mel+ with prospectively certain expression of the marker, giving subcutaneous xenograft in mice Balb/c nude. Objective: to evaluate the antitumor activity of lyo-SAV-RGD in vivo on human skin melanoma models melCher and MeWo with different melanogenesis ability and integrin avB3 expression. Both melanomas in vitro were shown to express integrin avB3 detected in melCher/mel+ cells with fluorescent-labeled rat antibodies Luc.H11 according to the expression component integrins avp3, p3-chain (CD61), and MeWo cells/mel- antibodies 23С6. In a high therapeutic total dose of 900 mg/kg, lyo-SAV-RGD inhibited growth of both melanomas in vivo with satisfactory tolerability. Compared to melCher/mel+, MeWo/mel-: T/Cmin=30% (p<0.05) versus T/ Cmin=50% (p=0.001) was more sensitive to treatment. The effect on melCher/mel+ was obtained only in the exponential phase of tumor growth. The results obtained allow us to consider it expedient to conduct an in-depth preclinical study of anti-integrin SAV-RGD, focused on the most aggressive disseminated amelanotic melanoma of the skin, regardless of the nature of blocking receptor expression.