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.
[1]Yangzhou Univ, Coll Med, Dept Clin Med, Yangzhou 225001, Jiangsu, Peoples R China.
[2]Yangzhou Univ, Coll Med, Vasc Biol Res Ctr, 11 Huaihai Rd, Yangzhou 225001, Jiangsu, Peoples R China.
[3]Yangzhou Univ, Jiangsu Key Lab Integrated Tradit Chinese & Weste, Yangzhou 225001, Jiangsu, Peoples R China.
[4]Yangzhou Univ, Jiangsu Coinnovat Ctr Prevent & Control Important, Yangzhou 225009, Jiangsu, Peoples R China.
[5]Yangzhou Univ, Mobile Postdoctoral Res Stn, Yangzhou, Jiangsu, Peoples R China.
[6]Shanghai Jiao Tong Univ, Dept Neurol, Affiliated People Hosp 6, South Campus, Shanghai 200233, Peoples R China.
[7]Jiamusi Univ, Affiliated Hosp 1, Dept Hematol, Jiamusi 154003, Heilongjiang, Peoples R China.
[8]Yangzhou Univ, Coll Med, Dept Anat, Yangzhou 225001, Jiangsu, Peoples R China.
(8.0+极速模式)