期刊
CELL BIOLOGY INTERNATIONAL
卷 46, 期 5, 页码 819-828出版社
WILEY
DOI: 10.1002/cbin.11778
关键词
chemokine (C-C motif) ligand 2; chemoresistance; glioma; glycolysis; temozolomide
类别
资金
- Zhejiang Basic Public Welfare Research Projects(Nature Science Foundation of Zhejiang province) [Q20H160004]
- Basic Research Program of Yunnan Province (key project of Kunming Medical Association)
- Yunnan Medical Leading Talents Project Fund [202001AY070001-160]
The study found that in temozolomide (TMZ)-resistant glioma cells, the expressions of CCL2 and CCR2 were significantly upregulated, and overexpression of CCL2 reduced the antitumor effect of TMZ by enhancing glycolysis.
The incidence of gliomas is increasing. Although great progress in glioma treatment has been made, the clinical outcome remains unsatisfactory. Chemokine (C-C motif) ligand 2 (CCL2) plays a key role in different types of cancers, including glioma. However, the function of CCL2 in glioma chemoresistance is not fully understood. In the current study, CCL2 was significantly upregulated in glioma. More importantly, CCL2 and CCR2 were significantly upregulated in temozolomide (TMZ)-resistant glioma. TMZ-resistant malignant glioblastoma cells (U251/TMZ) had higher expressions of CCL2 and CCR2 and a higher level of glycolysis as compared to its parental cell line U251. Silencing of CCL2 in U251/TMZ cells inhibited glycolysis. Overexpression of CCL2 reduced TMZ-induced apoptosis through activation of the AKT pathway and promotion of glycolysis. Moreover, overexpression of CCL2 significantly reduced the antitumor effect of TMZ in vivo. In conclusion, CCL2 overexpression reduced the antitumor effect of TMZ by enhancing glycolysis through activation of AKT signaling. The findings highlighted the importance of CCL2/CCR2/glycolysis and its potential value in developing new treatment for glioma.
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