title: Thiabendazole, a well-known antifungal drug, exhibits anti-metastatic melanoma B16F10 activity via inhibiting VEGF expression and inducing apoptosis.
abstract: Thiabendazole, an orally available antifungal drug, has been used in clinical practice for 40 years. Previous studies indicated its potential in inhibiting angiogenesis in both animal models and in human cells. Malignant melanoma is associated with angiogenesis and it is unknown whether thiabendazole is effective for malignant melanoma or not. In our research, the effects of thiabendazole on the proliferation of the murine metastatic melanoma cell line B16F10 in vitro and in vivo and the molecular mechanism were investigated. Assay of cell viability, chick embryo chorioallantoic membrane assay, quantitative real-time PCR, Western blot, wound healing assay, annexin V/propidium iodide (AV/PI) assay and B16F10-xenograft model were applied to elucidate the mechanism of thiabendazole on B16F10 cells. Thiabendazole inhibited B16F10 proliferation in vitro in a dose- and time-dependent manner with an IC50 of 532.4 +/- 32.6, 322.9 +/- 28.9, 238.5 +/- 19.8 microM at 24, 48, and 72 h, respectively. Moreover, thiabendazole inhibited the angiogenesis and the migration of B16F10 cells in vitro. Furthermore, thiabendazole restrained transcription and translation of the VEGF gene in B16F10 in vitro, and the apoptotic percentage of B16F10 cells was increased after exposure to thiabendazole. Finally, in the B16F10-bearing mice model, thiabendazole significantly suppressed tumor growth with inhibitory rates of 16.5%, 35.4% and 48.7% at the treatment of thiabendazole 20, 40 and 80 mg/kg, respectively. These results further indicated that thiabendazole may be a potential candidate for the treatment of malignant melanoma.
authors.affiliation: Department of Neurosurgery, Third Hospital, Jilin University, Changchun, Jilin, China.
authors.forename: Jinnan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Third Hospital, Jilin University, Changchun, Jilin, China.
authors.forename: Conghai
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, Third Hospital, Jilin University, Changchun, Jilin, China.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of General Surgery, Third Hospital, Jilin University, Changchun, Jilin, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, Third Hospital, Jilin University, Changchun, Jilin, China.
authors.forename: Huaxin
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of Neurosurgery, First Hospital, Jilin University, Changchun, Jilin, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000187:drug effects; D004396:Coloring Agents; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009368:Neoplasm Transplantation; D060888:Real-Time Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013827:Thiabendazole / Q000494:pharmacology*; D013844:Thiazoles; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000935:Antifungal Agents; D000970:Antineoplastic Agents; D004396:Coloring Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D042461:Vascular Endothelial Growth Factor A; C022616:thiazolyl blue; D013827:Thiabendazole