Cyphetrylin effect on somatostatin receptors expression in transplantable Ca-755 mice tumor

Abstract

Background. Expression evaluation of somatostatin receptors (SSTRs) in tumor cells is necessary for the reasonable use of therapy directed at such receptors.Aim. The affinity determination of the original analogue of somatostatin cyphetrylin for SSTRs of transplanted mice mammary adenocarcinoma Ca-755.Materials and methods. Cyphetrylin was synthesized in the Chemical Synthesis Laboratory of the Research Institute of Experimental Diagnostics and Therapy of Tumors, N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia. Cyphetrylin in tablet form was administered orally at a therapeutic dose of 10 mg/kg for 7 days to female F1 (C57Bl/6 × DBA/2) tumor-grafted Ca-755 mice. Animals of the control group were not administreted with сyphetrylin. Tumor tissue samples were obtained from animals on the 9th and 14th days after Ca-755 transplantation and sent for immunohistochemical study, which was performed on serial paraffin sections by the immunoperoxidase method using primary antibodies to various types of SSTRs.Results. The high frequency of positive expression of SSTR1, SSTR2, and SSTR5 (in 80, 100 and 100 % of tumor samples, respectively) was shown in tumor samples of the control group animals. As a result of cyphetrylin introduction in tumor samples obtained on the 9th day after Ca-755 inoculation, a change in the tumor receptor status was found towards a decrease in the level of expression of SSTR2 (80 % of samples) and SSTR5 (80 % of samples); SSTR1 expression did not change (80 % of samples). Compared to the controlled, in tumor samples after cyphetrylin administration, obtained on day 14 from Ca-755 transplantation, a decrease in the expression level of SSTR2 (80 % of samples), SSTR1 and SSTR5 (60 % of samples for SSTR each type) was noted, due to cyphetrylin binding to SSTRs of tumor cells. The receptors SSTR3 and SSTR4 did not show a high level of expression in the studied Ca-755 tumor samples.Immunohistochemical staining of Ca-755 cells with antibodies to SSTRs showed a tendency to reduction of antigen-positive cells number from 15–50 % in control to 10–40 % on day 9 after Ca-755 transplantation and 10–30 % on day 14 after Ca-755 transplantation.Conclusion. The data obtained indicates the presence in mice transplanted mammary adenocarcinoma Ca-755 of SSTR1, SSTR2 and SSTR5 high level expression due to the binding to which the direct cyphetrylin antitumor effect is realized.