Analysis of pro-inflammatory responses in neuroblastoma chemoresistance

Abstract

Neuroblastoma is the most frequent extra-cranial solid tumour occurring in infancy (Brodeur & Maris, 2006) accounting for 12% of cancer deaths and about 4% of malignancies in paediatric patients (Smith et al., 2010). High disease mortality is associated with aggressive neuroblastoma, commonly as a result of acquired chemoresistance and refractoriness to treatment. Inflammation is currently considered a hallmark of cancer and growing research is further highlighting its importance in cancer progression and chemoresistance. Studies on inhibition of inflammation have been shown to slow cancer progression, including neuroblastoma. In view of the current knowledge, the correlation of inflammation and chemoresistance was attempted by RTqPCR techniques using MIQE guidelines (Bustin et al., 2009). Two neuroblastoma cell lines were cultured in increasing doses of cytotoxic drugs to confer chemoresistance. mRNA was harvested and reverse transcribed to cDNA following gene expression analysis by qPCR to absolutely quantify transcripts of prostaglandin-endoperoxidase 2 (PTGS2), IL-8 and its receptors (CXCR1 and CXCR2). Whereas attenuation of chemoresistance in the cell models was successful, qPCR was not sufficiently robust and did not yield a positive correlation between chemoresistance and expression of target genes. Nonetheless, as a result of the assay limitations, absence of target gene expression still cannot be excluded.