我们在仓鼠中和体外观察了将二甲基苯并[b]呋喃和二甲基双胍以等效人用剂量联合应用是否能增强其对成纤维肉瘤的抗肿瘤活性。进行救治实验以检验甲苯硫丝唑（mebendazole）通过促进细胞存活的NF-κB激活是否能逆转治疗的抗肿瘤效果。将BHK-21/C13细胞培养物皮下接种到叙利亚金黄仓鼠中，并将其随机分为以下组别（每组6只动物）：1）未处理对照组；每日接受2）二甲基苯并[b]呋喃治疗；3）二甲基双胍治疗；4）二甲基苯并[b]呋喃和二甲基双胍在不同剂量的联合应用；5）二甲基苯并[b]呋喃、二甲基双胍和甲苯硫丝唑的联合应用；6）甲苯硫丝唑治疗。制作了二甲基苯并[b]呋喃和二甲基双胍联合应用的剂量-反应曲线。比较了不同组别的肿瘤生长动力学、生物物理学、病理学、组织学和免疫组织化学特征、切除瘤和仓鼠器官以及生化学和血液学血液检测。单一治疗没有抗肿瘤效果。二甲基苯并[b]呋喃（60 mg/kg/day）与二甲基双胍（500 mg/kg/day）对所有肿瘤生长参数具有显著（P < 0.05）的协同抑制效应，而且没有毒性作用，对生化学和血液学血液检测结果无影响。双倍剂量的二甲基苯并[b]呋喃和二甲基双胍联合应用得出相同的结果。甲苯硫丝唑的加入逆转了二甲基苯并[b]呋喃和二甲基双胍联合应用对肿瘤扩展的抑制作用。此外，二甲基苯并[b]呋喃和二甲基双胍在仓鼠成纤维肉瘤BHK-21/C13、人肺癌A549（CCL-185）、结肠癌HT-29（HTB-38）和宫颈癌HeLa（CCL-2）细胞培养中显示出抗增殖作用，并且对正常胎儿肺细胞MRC-5的细胞毒性明显较低。总而言之，二甲基苯并[b]呋喃和二甲基双胍联合应用在可达到人体剂量时可能推荐用于肿瘤学，因为其具有协同的抗肿瘤效果。©2023年作者发表。由Elsevier Masson SAS出版。保留所有权利。

We examined whether combinig diclofenac and metformin in doses equivalent to human doses would synergize their anticancer activity on fibrosarcoma inoculated to hamsters and in vitro. Rescue experiment was performed to examine whether the prosurvival NF-κB stimulation by mebendazole can reverse anticancer effects of the treatment. BHK-21/C13 cell culture was subcutaneously inoculated to Syrian golden hamsters randomly divided into groups (6 animals per group): 1) untreated control; treated daily with 2) diclofenac; 3) metformin; 4) combinations of diclofenac and metformin at various doses; 5) combination of diclofenac, metformin and mebendazole; 6) mebendazole. Dose response curves were made for diclofenac and metformin combination. Tumor growth kinetics, biophysical, pathological, histological and immunohistochemical characteristics of excised tumors and hamster organs as well as biochemical and hematological blood tests were compared among the groups. Single treatments had no anticancer effects. Diclofenac (60 mg/kg/day) exhibited significant (P < 0.05) synergistic inhibitory effect with metformin (500 mg/kg/day) on all tumor growth parameters, without toxicity and influence on biochemical and hematological blood tests. The same results were obtained with double doses of diclofenac and metformin combination. The addition of mebendazole to the diclofenac and metformin combination rescued tumor expansion. Furthermore, diclofenac with metformin demonstrated antiproliferative effects in hamster fibrosarcoma BHK-21/C13, human lung carcinoma A549 (CCL-185), colon carcinoma HT-29 (HTB-38) and cervical carcinoma HeLa (CCL-2) cell cultures, with markedly lower cytotoxicity in the normal fetal lung MRC-5 cells. In conclusion, diclofenac and metformin combination may be recommended for potential use in oncology, due to synergistic anticancer effect in doses achievable in humans.Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.