Department of Histology and Embryology, Faculty of Medicine, University of Novi Sad, Novi Sad, Republic of Serbia.
Eur Rev Med Pharmacol Sci. 2018 Apr;22(8):2461-2467. doi: 10.26355/eurrev_201804_14840.
We investigated the effect of metformin and caffeine on fibrosarcoma in hamsters.
32 Syrian golden hamsters of both sexes, weighing approximately 100 g, were randomly allocated to 3 experimental and 2 control groups, with a minimum of 6 animals per group. 2 x 106 BHK-21/C13 cells in 1 ml were injected subcutaneously into the animals' back in 4 groups. The first experimental group started peroral treatment with metformin 500 mg/kg daily, the second with caffeine 100 mg/kg daily and the third with a combination of metformin 500 mg/kg and caffeine 100 mg/kg daily, via a gastric probe 3 days before tumor inoculation. After 2 weeks, when the tumors were approximately 2 cm in the control group, all animals were sacrificed. The blood was collected for glucose and other analyses. The tumors were excised and weighed and their diameters were measured. The tumor samples were pathohistologically (HE) and immunohistochemically (Ki-67, CD 31, COX IV, GLUT-1, iNOS) assessed and the main organs toxicologically analyzed, including the control animals that had received metformin and caffeine. Tumor volume was determined using the formula LxS2/2, where L was the longest and S the shortest diameter. Ki-67-positive cells in the tumor samples were quantified. Images were taken and processed by software UTHSCSA Image Tools for Windows Version 3.00. Statistical significances were determined by the Student's t-test.
The combination of metformin and caffeine inhibited fibrosarcoma growth in hamsters without toxicity.
Administration of metformin with caffeine might be an effective and safe approach in novel nontoxic adjuvant anticancer treatment.
研究二甲双胍和咖啡因对仓鼠纤维肉瘤的影响。
32 只雌雄各半、体重约 100g 的叙利亚金黄地鼠随机分为 3 个实验组和 2 个对照组，每组至少 6 只动物。4 组动物背部皮下注射 1ml 含 2×106 BHK-21/C13 细胞悬液。第 1 实验组在肿瘤接种前 3 天开始每天经胃管给予 500mg/kg 二甲双胍，第 2 实验组每天给予 100mg/kg 咖啡因，第 3 实验组给予 500mg/kg 二甲双胍和 100mg/kg 咖啡因联合治疗。2 周后，当对照组肿瘤约 2cm 时，所有动物均处死。采集血液进行血糖等分析。切除肿瘤并称量，测量其直径。肿瘤标本行组织病理学（HE）和免疫组织化学（Ki-67、CD31、COX IV、GLUT-1、iNOS）评估，并对主要器官进行毒理学分析，包括接受二甲双胍和咖啡因的对照组动物。使用公式 LxS2/2 计算肿瘤体积，其中 L 为最长径，S 为最短径。对肿瘤标本中的 Ki-67 阳性细胞进行定量。通过 UTHSCSA Image Tools for Windows Version 3.00 软件对图像进行拍摄和处理。采用 Student's t 检验确定统计学意义。
二甲双胍和咖啡因联合应用可抑制仓鼠纤维肉瘤生长，且无毒性。
二甲双胍联合咖啡因给药可能是一种有效且安全的新型非毒性辅助抗癌治疗方法。
