Benzimidazole anthelmintics flubendazole and mebendazole are microtubule-targeting drugs that showed considerable anti-cancer activity in different preclinical models. In this study, the effects of flubendazole and mebendazole on proliferation, migration and cadherin switching were studied in a panel of oral cell lines in vitro. Both compounds reduced the viability of the PE/CA-PJ15 and H376 oral squamous carcinoma cells and of the premalignant oral keratinocytes DOK with the IC₅₀ values in the range of 0.19–0.26 μM. Normal oral keratinocytes and normal gingival fibroblasts were less sensitive to the treatment. Flubendazole and mebendazole also reduced the migration of the PE/CA-PJ15 cell in concentrations that had no anti-migratory effects on the normal gingival fibroblasts. Levels of the focal adhesion kinase FAK, Rho-A and Rac1 GTPases and the Rho guanine nucleotide exchange factor GEF-H1 were decreased in both PE/CA-PJ15 cells and gingival fibroblasts following treatment. Both drugs also interfered with cadherin switching in the model of TGF-β-induced epithelial to mesenchymal transition (EMT) in the DOK cell line. Levels of N-cadherin were reduced in the TGF-β induced cells co-treated with flubendazol and mebendazole in very low concentration (50 nM). These results suggest direct effects of both benzimidazoles on selected processes of EMT in oral cell lines such as cadherin switching as well as cellular migration.

苯并咪唑驱虫药氟苯达唑和甲苯达唑是靶向微管的药物，在不同的临床前模型中显示出显着的抗癌活性。在这项研究中，在一组口腔细胞系中体外研究了氟苯达唑和甲苯达唑对增殖，迁移和钙黏着蛋白转换的影响。两种化合物均通过IC ₅₀降低了PE / CA-PJ15和H376口腔鳞状细胞癌细胞以及口腔癌前角质形成细胞DOK的活力值在0.19–0.26μM的范围内。正常的口腔角质形成细胞和正常的牙龈成纤维细胞对治疗的敏感性较低。氟苯达唑和甲苯达唑还以对正常牙龈成纤维细胞无抗迁移作用的浓度降低了PE / CA-PJ15细胞的迁移。处理后，PE / CA-PJ15细胞和牙龈成纤维细胞中的黏着斑激酶FAK，Rho-A和Rac1 GTPases和Rho鸟嘌呤核苷酸交换因子GEF-H1的水平均降低。两种药物在TOK-β诱导的DOK细胞系上皮向间质转化（EMT）模型中也都干扰钙黏着蛋白的转换。在与氟苯达唑和甲苯达唑以非常低的浓度（50 nM）共同处理的TGF-β诱导的细胞中，N-钙黏着蛋白的水平降低。