The modern period of development of medicine is characterized by significant achievements in the field of creating medicines based on peptides, studying their clinical effectiveness and substantiating the appropriateness of using various diseases and pathological conditions in complex therapy. The study of the mechanisms of action of peptides acquires special significance in connection with the development of biological therapy of tumors aimed at enhancing the protective functions of the organism.
To evaluate the effect of natural and synthetic peptides on carcinogenesis, the effect of these peptide preparations on the growth of spontaneous, induced and transplanted tumors in experimental animals was studied.
The results of the studies indicate that the peptides have a pronounced protective effect in experimental carcinogenesis and have a modulating effect on the immune and neuroendocrine systems of the body in the tumor process.
The use of natural peptides in mice and rats contributed to a significant decrease in the frequency of development of spontaneous tumors by 1.5-2.5 times and an increase in the life span of animals by 30-40%. At the same time, there was also an increase in the indices of cellular immunity.
When studying the effect of natural peptides on the carcinogenesis induced by radiation exposure, the inhibitory effect of drugs on the growth of tumors was clearly established. The number of rats that developed malignant tumors in the experimental group was 1.9-2.7 times less than in the control group. The median latent period of the onset of tumors in the group of rats receiving natural peptides was on average 2 months longer than in the controls.
In irradiated mice treated with natural peptides, the incidence of all tumors was 28%, whereas in irradiated animals in control, this was 92%. The number of malignant tumors decreased with the administration of drugs 10 times.
The effect of natural peptides on chemical carcinogenesis was investigated in the rat adenocarcinoma model of rats induced by the administration of 7,12-dimethylbenz (a) anthracene. In control animals under the influence of a carcinogen, adenocarcinomas of the breast developed in 80% of cases, and when the peptides were introduced, only in 25%. At the same time, the multiplicity of adenocarcinoma decreased 3 times.
Important results for the evaluation of antimutagenic and anticarcinogenic properties of peptide preparations have the results obtained in the study of their effect on transplacental carcinogenesis in rats that were exposed to nitrosoethylurea during pregnancy. As is known, when nitrosoethylurea is administered to female rats, glial tumors of the central nervous system and peripheral nerve nerves develop at a high frequency in the offspring. The introduction of natural peptides promoted an increase in the latent period of tumor development by an average of 2 months, a decrease in the index of tumor multiplicity by 1.4 times, a decrease in the frequency of neoplasms of the spinal cord and kidneys, and an increase in the life span of animals.
The data that natural peptides cause inhibition of carcinogenesis and an increase in the life span of laboratory animals have served as the basis for studying the effect of synthetic peptides (analogues of endogenous) on these parameters.
The use of di- and tetrapeptides exerted a depressing effect on spontaneous carcinogenesis in mice, which was expressed in a 1.5-fold decrease in the incidence of all tumors and in 1.9 times the multiplicity of tumors. The survival dynamics in all the study groups of animals did not differ significantly until the age of 22 months, after which a clear decrease in mortality was observed under the influence of peptides.
When the dipeptide was administered to rats exposed to radioactive radiation from a mixture of 90Sr and 137Cs, inhibition of the development of malignant tumors was observed, in particular, a reduction in the incidence of adenocarcinoma of the mammary gland. In this case, an increase in the maximum life expectancy by 4.6 months was observed in comparison with the animals in the control group.
It was found that the tetrapeptide suppressed the growth of colon tumors induced by 1,2-dimethylhydrazine. The effect of this drug was expressed in reducing the multiplicity of tumors and their size.
When studying the effect of synthetic peptides on the occurrence and development of cancer of the bladder induced by the carcinogen of the selective action of N-butyl-N- (4-hydroxybutyl) nitrosamine, it was found that 56% of the animals developed the tumor dipeptide, while in the control group - in 75.5% of cases. With the action of the drug, there was a 2-fold decrease in the development of preneoplastic and early neoplastic changes in the mucous membrane of the bladder and a significant inhibition of carcinogenesis. The action of the dipeptide led to the inhibition of both the initiation of carcinogenesis and the promotion, i. E. realization of the tumor process.
Synthetic di- and tetrapeptides when administered to animals with transplanted hepatoma had a significant inhibitory effect at an early stage after inoculation of tumor cells. When studying the effect of peptides on the growth of the tumor, ACATOL, their inhibitory effect was also established. The use of synthetic peptides during the latent period led to a significant slowing of the growth rate of the transplanted sarcoma M-1. The inhibitory effect was manifested 2 weeks after the termination of the course of the peptide administration and was maintained for the entire observation period. In addition, it was found that after the use of peptides, the level of apoptotic death of tumor cells increased.
The effect of synthetic peptides on carcinogenesis was examined in females of transgenic mice bearing the breast cancer gene. The number of animals in which mammary tumors did not develop, in the group receiving tetrapeptide, was 1.6 times more than in the control. The maximum size of mammary adenocarcinoma in mice treated with this peptide was 33% less than in controls. The expression of the oncogene in mammary tumors of mice treated with tetrapeptide was reduced 3.7-fold compared to the same index in tumors of control mice.
Experimental studies of the antitumor effect of natural and synthetic peptides testify to the effect of these drugs on mechanisms of carcinogenesis and the prospects of their use in cancer patients.
Due to the fact that natural peptides contribute to the restoration of cellular immunity and hormonal regulation, and also have an antitumor effect, these drugs were used in cancer patients mainly with hormone-dependent forms of tumors (breast, body or cervical cancer, ovaries and other localization). All patients underwent histological verification of the tumor process. Most subjects were subjected to a combined or complex treatment.
Natural peptides were used in patients with breast cancer II-III stage on the background of radiation therapy. The drugs were prescribed according to various schemes: after the end of radiotherapy, in the middle of the course and in the last 5-10 days of preoperative radiotherapy. In some patients, peptides were applied in the long term after the radiation therapy (after 2-6 months) due to the development of persistent leukopenia and lymphopenia, which can not be corrected by other drugs. The introduction of peptides to patients with breast cancer promoted an increase in the number of lymphocytes and T-lymphocytes in the blood. In addition, in patients after immunocorrection, the functional activity of T cells was improved and the intensity of cellular immunity responses was restored. The introduction of drugs to patients in the long term after irradiation caused an increase in the number of leukocytes in the blood. The parameters of cellular immunity after the use of drugs have almost normalized.
In clinical studies conducted in patients with cervical cancer receiving natural peptides, there was an increase in the number and functional activity of T lymphocytes in peripheral blood. The administration of drugs to patients with cervical cancer who received radiation treatment or chemotherapy had a pronounced protective effect on hemopoiesis, prevented the development of leukopenia, thrombocytopenia, as well as inflammatory postoperative complications.
The results of the studies testify to the prospects of using combined progestin therapy and immunotherapy in primary patients with endometrial cancer. The study of the effect of natural peptides on immunological parameters in patients with endometrial cancer after preoperative hormone therapy showed that treatment leads to a significant increase in the absolute number of lymphocytes and T-lymphocytes. Simultaneously, restoration of the functional activity of T-lymphocytes was observed.
The results of an experimental study of the effect of synthetic peptides on the growth of spontaneous, induced and transplanted tumors also served as the basis for the use of these drugs in cancer patients.
The use of dipeptide in patients with colorectal cancer over the age of 50 years with surgical and complex treatment, as well as its use against the background of the generalization of the tumor process that has developed after previous radical treatment, contributes to the normalization of the immune status of patients, reducing the number of side effects and toxic effects of chemotherapy. The use of 3 courses of the drug in patients of this category in the first 6 months after radical treatment caused a significant decrease in the incidence of relapse and generalization of the tumor in the next 2 years.
Dipeptide was used in patients with breast cancer against high-dose polychemotherapy. During the follow-up (22 months) positive results were observed in 100% of patients, no relapses and metastases were detected. At the same time, during this period in the control group with the tradition