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Journal №10 for 2011 г.
Article in number:
Antitumor Effect of the Somatostatin Analogue Cifetrelin in Vivo
Keywords: somatostatin somatostatin analogue breast cancer cervical carcinoma
Authors:
Е.I. Mikhaevich, N.P. Yavorskaya, I.S. Golubeva, N.A. Oborotova, R.N. Alyautdin
Abstract:
The studying of somatostatin effects has started in 1970s. Somatostatin was found to be widespread in nervous system and gastrointestinal tract. This hormone has a various biological activities: it inhibits the release of growth hormone, insulin, glucagon, cholecystokinin, pancreatic hormones, gastric juices; besides, somatostatin inhibits the proliferation of normal and tumor cells. Because of the instability of native somatostatin (half lifetime is 3 minutes) it is impossible to use it as antitumor agent and all researches are focused on the synthetic somatostatin analogues, some of which are successfully used in chemotherapy. Obvious benefits of the use of somatostatin analogues as antitumor agents are the wide spectrum of inhibitory and antiproliferative effects and minor side effects. Today the effectiveness of somatostatin analogues in the symptomatic therapy of secreting endocrine tumors of gastrointestinal tract (carcinoid, vipoma, glucagonoma, gastrinoma, insulinoma) and neuroendocrine tumors is proved. Also there are evidences of the effectiveness of such compounds in the therapy of breast cancer, pancreatic carcinoma, human small cell lung carcinoma. It may be said that somatostatin analogues give the opportunity to treat different types of neoplasms. The novel somatostatin analogues are being continuously searched and studied. In the laboratory of chemical synthesis of Institute of experimental diagnostics and chemotherapy of Russian N.N.Blokhin Cancer Research Centre RAMS a novel somatostatin analogue, cifetrelin, a noncyclic pentapeptide, was synthesized. The aim of this study was to evaluate antitumor activity of cifetrelin and to reveal its optimal dose and the route of administration. We have shown that cifetrelin has a wide spectrum of antitumor activity - it had a cytostatic effect on cervical carcinoma, lung carcinoma, breast cancer and adenocarcinoma of large intestine. Antitumor effect of cifetrelin was dose-independent in the studied dosage range (0,1 mg/kg to 120 mg/kg). We have revealed that doses of 0,1 mg/kg to 120 mg/kg are nontoxic. The optimal therapeutic dose was a dose of 1 mg/kg of animal body weight. The most beneficial route of administration was a peroral route. In general the results of this study demonstrate the expediency of further study of the antitumor effects of cifetrelin, administered perorally, having the development of peroral drug formulation of cifetrelin in sight.
Pages: 68-73
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