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Glioma cells escaped from cytotoxicity of temozolomide and vincristine by communicating with human astrocytes
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  • 作者:Weiliang Chen (1) (2)
    Donghai Wang (1)
    Xinwen Du (3)
    Ying He (2)
    Songyu Chen (1) (2)
    Qianqian Shao (2)
    Chao Ma (2)
    Bin Huang (1)
    Anjing Chen (1)
    Peng Zhao (1)
    Xun Qu (2)
    Xingang Li (1)

    1. Department of Neurosurgery
    ; Qilu Hospital of Shandong University and Brain Science Research Institute ; Shandong University ; Jinan ; 250012 ; China
    2. Institute of Basic Medical Sciences
    ; Qilu Hospital of Shandong University ; Jinan ; China
    3. Department of Pediatric Surgery
    ; Laizhou People鈥檚 Hospital ; Yantai ; China
  • 关键词:Astrocyte ; Chemoresistance ; Glioma ; Temozolomide ; Vincristine
  • 刊名:Medical Oncology
  • 出版年:2015
  • 出版时间:March 2015
  • 年:2015
  • 卷:32
  • 期:3
  • 全文大小:4,385 KB
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  • 刊物主题:Oncology; Hematology; Pathology; Internal Medicine;
  • 出版者:Springer US
  • ISSN:1559-131X
文摘
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.

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