Abstract:

Objective In this study，we aimed to use cDNA microarrays to identify differentially expressed genes and activation or inhibition of signaling pathways that may account for the phenotype of rituximab-resistant cell lines. Methods Rituximab-resistant B-cell non-Hodgkin′s lymphoma cell lines were established，and cDNA microarray analysis was performed on the resistant and parental cell lines. Bioinformatics analysis was carried out using the KEGG database and DAVID software. Results We identified 70 genes that were up-regulated and 42 that were down-regulated in both Jeko-1/R and Raji/R resistant cell lines compared to parental lines. KEGG pathway analysis suggested that the MAPK signaling pathway is significantly more active in Jeko-1/R and Raji/R cells. GO term analysis of differentially expressed genes suggested that rituximab-resistant cells show the characteristics of “anti-apoptosis”， “promoting proliferation” and “blood vessel development”. Conclusion Our results suggest that rituximab resistance is most closely associated with the MAPK signaling pathway， which may act to inhibit apoptosis and promote proliferation and vascular development. These findings provide a theoretical basis for predicting and overcoming rituximab resistance in the clinical setting.

Key words: Lymphoma, Rituximab, Drug resistance, cDNA microarray, MAPK signaling pathway, Bioinformatics