Glioma cells escaped from cytotoxicity of temozolomide and vincristine by communicating with human astrocytes

被引：91

作者：

Chen, Weiliang ^{[1
,2
,3
]}

Wang, Donghai ^{[1
,2
]}

Du, Xinwen ^{[4
]}

He, Ying ^{[3
]}

Chen, Songyu ^{[1
,2
,3
]}

Shao, Qianqian ^{[3
]}

Ma, Chao ^{[3
]}

Huang, Bin ^{[1
,2
]}

Chen, Anjing ^{[1
,2
]}

Zhao, Peng ^{[1
,2
]}

Qu, Xun ^{[3
]}

Li, Xingang ^{[1
,2
]}

机构：

[1] Shandong Univ, Qilu Hosp, Dept Neurosurg, Jinan 250012, Peoples R China

[2] Shandong Univ, Brain Sci Res Inst, Jinan 250012, Peoples R China

[3] Shandong Univ, Qilu Hosp, Inst Basic Med Sci, Jinan 250012, Peoples R China

[4] Laizhou Peoples Hosp, Dept Pediat Surg, Yantai, Peoples R China

来源：

MEDICAL ONCOLOGY | 2015年 / 32卷 / 03期

基金：

中国国家自然科学基金;

关键词：

Astrocyte; Chemoresistance; Glioma; Temozolomide; Vincristine; GAP-JUNCTION COMMUNICATION; TUMOR-STROMA INTERACTIONS; MALIGNANT GLIOMA; REACTIVE ASTROCYTES; CHEMOTHERAPY; CONNEXIN-43; RESISTANCE; APOPTOSIS; SURVIVAL; MICROENVIRONMENT;

D O I：

10.1007/s12032-015-0487-0

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Resistance to chemotherapeutic drugs remains a great obstacle to successful treatment of gliomas. Understanding the mechanism of glioma chemoresistance is conducive to develop effective strategies to overcome resistance. Astrocytes are the major stromal cells in the brain and have been demonstrated to play a key role in the malignant phenotype of gliomas. However, little is known regarding its role in glioma chemoresistance. In our study, we established a co-culture system of human astrocytes and glioma in vitro to simulate tumor microenvironment. Our results showed that astrocytes significantly reduced glioma cell apoptosis induced by the chemotherapeutic drugs temozolomide and vincristine. This protective effect was dependent on direct contact between astrocytes and glioma cells through Cx43-GJC. Moreover, in human glioma specimens, we found astrocytes infiltrating around the tumor, with a reactive appearance, suggesting that these astrocytes would play the same chemoprotective effect on gliomas in vivo. Our results expand the understanding of the interaction between astrocytes and glioma cells and provide a possible explanation for unsatisfactory clinical outcomes of chemotherapeutic drugs. Cx43-GJC between astrocytes and glioma cells may be a potential target for overcoming chemoresistance in gliomas clinically.

引用

页数：13

共 46 条

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Upregulation of gap junctional intercellular communication and connexin 43 expression by cyclic-AMP and all-trans-retinoic acid is associated with glutathione depletion and chemosensitivity in neuroblastoma cells [J].