OIP5 Expression Sensitize Glioblastoma Cells to Lomustine Treatment
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.
KeywordsGlioblastoma OIP5 Lomustine Drug resistance
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.
This work was approved by the ethics committees of the São Paulo Federal University (CEP-UNIFESP) number 1015/11.
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