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OIP5 Expression Sensitize Glioblastoma Cells to Lomustine Treatment

  • Dorival Mendes Rodrigues-Junior
  • Thaís Priscila Biassi
  • Viviane Carlin
  • Marcus Vinicius Buri
  • Ana Claudia Torrecilhas
  • Karina Ramalho Bortoluci
  • André Luiz Vettore
Article

Abstract

Glioblastoma (GBM) is an incurable disease ranked among the deadliest solid cancers worldwide. A better understanding on the molecular aspects of this malignancy could contribute to the development of new treatment strategies and help to improve survival rates. Previously, our group had shown that GBM patients expressing the cancer/testis antigen Opa Interacting Protein 5 (OIP5) present a longer survival period than the OIP5-negative group. The main goal of this study was to evaluate the OIP5 contribution to GBM tumorigenesis and assess the role of OIP5 in GBM cell response to lomustine, an alkylating agent used in the treatment of this malignancy. So, the effect of OIP5 knockdown was evaluated in A172 and T98G GBM cell lines. Our results demonstrated that downregulation of the OIP5 stimulates glioma cell viability and inhibits cell death-induced necrosis prompted by lomustine. In conclusion, our data shows that OIP5 expression in GBM cells seems to be able to enhance lomustine cytotoxic effects, reinforcing that this gene is a potential therapeutic target and putative molecular biomarker for treatment response in GBM.

Keywords

Glioblastoma OIP5 Lomustine Drug resistance 

Notes

Financial Support

This study was funded by São Paulo Research Foundation (FAPESP grant 2012/14837-7; 2010/20218-2). TPB and DMR-Jr received a scholarship from São Paulo Research Foundation (FAPESP, 2011/15118-1 and 2012/01597-8, respectively). ALV has a National Counsel of Technological and Scientific Development scholarship (CNPq, 300936/2015-0).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

This work was approved by the ethics committees of the São Paulo Federal University (CEP-UNIFESP) number 1015/11.

Supplementary material

12031_2018_1184_MOESM1_ESM.doc (31 kb)
ESM 1 (DOC 31 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Dorival Mendes Rodrigues-Junior
    • 1
  • Thaís Priscila Biassi
    • 1
  • Viviane Carlin
    • 1
  • Marcus Vinicius Buri
    • 2
  • Ana Claudia Torrecilhas
    • 3
  • Karina Ramalho Bortoluci
    • 1
  • André Luiz Vettore
    • 1
    • 4
  1. 1.Department of Biological ScienceUniversidade Federal de São PauloDiademaBrazil
  2. 2.Department of BiochemistryUniversidade Federal de São PauloSão PauloBrazil
  3. 3.Department of Pharmaceutical ScienceUniversidade Federal de São PauloDiademaBrazil
  4. 4.Laboratório de Biologia Molecular do CâncerUNIFESPSão PauloBrazil

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