title: Temozolomide inhibits cellular growth and motility via targeting ERK signaling in glioma C6 cells.
abstract: Temozolomide (TMZ) is an alkylating agent used for the treatment of aggressive forms of brain tumor based on its antitumor actions. However, the exact effect on cancer and the underlying anticancer molecular mechanism of TMZ remain to be elucidated. In the present study, the effects of TMZ on the growth and motility of glioma C6 cells were investigated. MTT and Transwell assays were used to detect cellular growth and motility. The results showed that TMZ inhibited the proliferation, migration and invasion of the glioma C6 cells in vitro, western blot analysis determined that the phosphorylation of extracellular signal‑regulated protein kinase (ERK)1/2 was decreased in the TMZ‑treated cells, compared with the untreated control cells. The ERK1/2 specific inhibitor, U0126, augmented the inhibitory effects of TMZ on the proliferation, migration and invasion of the glioma C6 cells, and the mitogen‑activated protein kinase kinase/ERK pathway activator, curcumin, attenuated the inhibitory effects of TMZ on the proliferation and motility of the glioma C6 cells. Additionally, the western blotting in the present study demonstrated that TMZ and U0126 decreased the expression of vascular endothelial growth factor-C (VEGF-C), and the expression level was restored by curcumin, suggesting that VEGF‑C may be the downstream effector of ERK1/2. Furthermore, the overexpression of VEGF‑C enhanced the growth, migration and invasion of the TMZ-treated cells. These results suggested that TMZ suppressed glioma C6 cell development, at least in part, and downregulated the expression of VEGF‑C by inhibiting the ERK signaling pathway. The results of the present study provides the foundation for a combinational therapeutic strategy to improve the efficacy of TMZ.
authors.affiliation: Department of Clinical Medicine, College of Medicine, Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China.
authors.forename: Yingge
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurological, Shanghai JiaoTong University Affiliated The Sixth People Hospital, South Campus, Shanghai 200233, P.R. China.
authors.forename: Shan
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Hematology, First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154003, P.R. China.
authors.forename: Weiguang
authors.initials: W
authors.lastname: Wang
authors.affiliation: The Research Center for Vascular Biology, College of Medicine, Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China.
authors.forename: Jingyan
authors.initials: J
authors.lastname: Liang
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015870:Gene Expression; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D010641:Phenotype; D010766:Phosphorylation; D051381:Rats; D000077204:Temozolomide; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics / Q000378:metabolism
chemical_list: D018906:Antineoplastic Agents, Alkylating; D042582:Vascular Endothelial Growth Factor C; D003606:Dacarbazine; D000077204:Temozolomide