OIP5 Expression Sensitize Glioblastoma Cells to Lomustine Treatment

J Mol Neurosci. 2018 Nov;66(3):383-389. doi: 10.1007/s12031-018-1184-1. Epub 2018 Oct 3.

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: Drug resistance; Glioblastoma; Lomustine; OIP5.

MeSH terms

  • Antineoplastic Agents, Alkylating / pharmacology
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosomal Proteins, Non-Histone / metabolism
  • Drug Resistance, Neoplasm / genetics*
  • Glioblastoma / metabolism*
  • Humans
  • Lomustine / pharmacology

Substances

  • Antineoplastic Agents, Alkylating
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • OIP5 protein, human
  • Lomustine