Association of decreased levels of lipopolysaccharide-binding protein with OKN-007-induced regression of tumor growth in an F98 rat glioma model

J Neurosurg. 2019 Oct 18;133(6):1695-1703. doi: 10.3171/2019.7.JNS182435.

Abstract

Objective: High-grade gliomas, such as glioblastoma (GBM), are devastating tumors with a very poor prognosis. Previously the authors have found that the nitrone compound OKN-007 (OKlahoma Nitrone 007; or disodium 4-[(tert-butyl-imino) methyl] benzene-1,3-disulfonate N-oxide) is effective against high-grade gliomas in various GBM rodent and human xenograft models. The purpose of the present study was to assess the levels of the lipopolysaccharide-binding protein (LBP) in rodent gliomas treated with OKN-007 as well as determine the expression of LBP in human gliomas.

Methods: Microarray analysis was done to assess altered gene expression following OKN-007 administration in an F98 glioma model. An enzyme-linked immunosorbent assay was incorporated to assess LBP levels in glioma tissues, as well as blood serum, comparing results in OKN-007-treated and untreated tumor-bearing animals. Immunohistochemistry was used to assess LBP levels in varying grades of human glioma tissue sections.

Results: Upon further assessment of gene expression fold changes in F98 gliomas in rats that received or did not receive OKN-007, it was found that the gene for LBP was significantly downregulated by OKN-007. Further investigation was done to see whether levels of LBP were affected by OKN-007 treatment in F98 gliomas. It was found that LBP could be detected not only in glioma tissue but also in blood serum of F98 glioma-bearing rats and that OKN-007 decreased the levels of LBP. It was also found that LBP levels are highly expressed in human high-grade glioma tissues.

Conclusions: LBP could potentially be used as a serum diagnostic marker of treatment response in high-grade gliomas.

Keywords: F98 rat glioma; GBM; OKN-007; glioblastoma; high-grade gliomas; lipopolysaccharide-binding protein; oncology.