PMID- 27878252
OWN - NLM
STAT- MEDLINE
DCOM- 20170406
LR  - 20181202
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Linking)
VI  - 14
IP  - 6
DP  - 2016 Dec
TI  - Temozolomide inhibits cellular growth and motility via targeting ERK signaling in 
      glioma C6 cells.
PG  - 5732-5738
LID - 10.3892/mmr.2016.5964 [doi]
AB  - 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.
FAU - Wang, Yingge
AU  - Wang Y
AD  - Department of Clinical Medicine, College of Medicine, Yangzhou University, 
      Yangzhou, Jiangsu 225001, P.R. China.
FAU - Gao, Shan
AU  - Gao S
AD  - Department of Neurological, Shanghai JiaoTong University Affiliated The Sixth 
      People Hospital, South Campus, Shanghai 200233, P.R. China.
FAU - Wang, Weiguang
AU  - Wang W
AD  - Department of Hematology, First Affiliated Hospital of Jiamusi University, 
      Jiamusi, Heilongjiang 154003, P.R. China.
FAU - Liang, Jingyan
AU  - Liang J
AD  - The Research Center for Vascular Biology, College of Medicine, Yangzhou 
      University, Yangzhou, Jiangsu 225001, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20161123
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Antineoplastic Agents, Alkylating)
RN  - 0 (Vascular Endothelial Growth Factor C)
RN  - 7GR28W0FJI (Dacarbazine)
RN  - YF1K15M17Y (Temozolomide)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents, Alkylating/*pharmacology
MH  - Brain Neoplasms/genetics/*metabolism/pathology
MH  - Cell Line, Transformed
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Dacarbazine/*analogs & derivatives/pharmacology
MH  - Gene Expression
MH  - Glioma/genetics/*metabolism/pathology
MH  - Humans
MH  - MAP Kinase Signaling System/*drug effects
MH  - Phenotype
MH  - Phosphorylation
MH  - Rats
MH  - Temozolomide
MH  - Vascular Endothelial Growth Factor C/genetics/metabolism
EDAT- 2016/11/24 06:00
MHDA- 2017/04/07 06:00
CRDT- 2016/11/24 06:00
PHST- 2015/08/15 00:00 [received]
PHST- 2016/08/08 00:00 [accepted]
PHST- 2016/11/24 06:00 [pubmed]
PHST- 2017/04/07 06:00 [medline]
PHST- 2016/11/24 06:00 [entrez]
AID - 10.3892/mmr.2016.5964 [doi]
PST - ppublish
SO  - Mol Med Rep. 2016 Dec;14(6):5732-5738. doi: 10.3892/mmr.2016.5964. Epub 2016 Nov 
      23.