Anisimov V N, Popovich I G, Egormin P A, Tyndyk M L, Yurova M N, Osipov M A
Vopr Onkol. 2016;62(2):234-44.
The critical analysis of preclinical testing of anticarcinogenic and antitumor activity of biguanides presented in this paper. Experiments have been conducted using in total more than 20 models of carcinogenesis including models of spontaneous , chemically- , radiation- and virus-induced carcinogenesis, as well as carcinoigenesis induced by special fat diets and by genetic modification in rodents. Cancer preventive effect of buiguanides has been studied in relation to total tumor incidence and to 17 target organs in animals of 3 species, including 25 various strains of mice, 4 strains of rats and 1 strain of hamsters using various routs of administration and doses. In the majority of cases (86%) the exposure to biguanides leads to inhibition of carcinogenesis. In 14% of the cases inhibitory effect of the drugs was not observed, however there was no any case of stimulation of carcinogenesis by antidiabetic biguanides., Metformin suppressed tumor growth in the majority of in vitro studies conducted in 46 different cell lines originated from malignant tumors of 15 localization as well as in athymic mice with xenografts of 31 tumor lines. It was concluded that there are sufficient experimental evidences of anticarcinogenic and antitumor effects of antidiabetic biguanides revealed in a number of models of induced and spontaneous carcinogenesis.
本文对双胍类化合物抗癌和抗肿瘤活性的临床前试验进行了批判性分析。已使用总共20多种致癌模型进行了实验，包括自发、化学、辐射和病毒诱导的致癌模型，以及由特殊脂肪饮食和啮齿动物基因改造诱导的致癌模型。研究了双胍类化合物对3个物种动物的总肿瘤发生率和17个靶器官的癌症预防作用，包括25种不同品系的小鼠、4种品系的大鼠和1种品系的仓鼠，采用了不同的给药途径和剂量。在大多数情况下（86%），接触双胍类化合物会导致致癌作用受到抑制。在14%的病例中未观察到药物的抑制作用，然而，没有任何病例显示抗糖尿病双胍类化合物会刺激致癌作用。在对源自15个部位恶性肿瘤的46种不同细胞系以及具有31种肿瘤系异种移植的无胸腺小鼠进行的大多数体外研究中，二甲双胍抑制了肿瘤生长。得出的结论是，在许多诱导和自发致癌模型中揭示的抗糖尿病双胍类化合物的抗癌和抗肿瘤作用有充分的实验证据。
