The Anti-invasive Effect And Mechanism Of Novel Nucleoside Analogue (FNC) On Aggressive Non-hodgkin’s Lymphoma

Background and Objective:Malignant lymphoma (ML) belongs to the immune tumor of lymphoid tissuelocated in and/or external the lymph nodes. According to the pathological types,malignant lymphoma is usually divided into two groups. They are Hodgkin’slymphomas (HL) and non-Hodgkin’s lymphoma (NHL). NHL accounts for90%inthe total number of malignant lymphoma approximately, and about70%of NHL isB-NHL. In the comprehensive treatment of aggressive NHL, the dominant treatmentis chemotherapy. However, their treatment effect is not very satisfactory. Therefore,there is an urgent need to develop more effective and less side-effectiveanti-lymphoma medications.FNC（2’-deoxy-2’-β-fluoro-4’-azidocytidine）, a novel nucleoside analogue, wassynthesized by Zhengzhou College of Chemistry and Molecular Engineering. Andfurthermore, FNC has applied for a national patent for invention. The patent numberis ZL201010506595.X. The previous research was displayed that FNC had asignificantly inhibitory effect on proliferation of several B-NHL cells, showing agood development potential. In order to further research, Raji cells and JeKo-1cellswhich belong to highly invasive B-NHL cells were chosen to explore theanti-invasive effect and mechanism of novel nucleoside analogue (FNC) onaggressive non-Hodgkin’s lymphoma. Methods:Raji and JeKo-1cells were treated by FNC in different concentrations for24h(Raji with FNC of0.035,0.175,0.875,4.375μmol·L-1; JeKo-1with FNC of0.0016,0.008,0.04,0.2μmol·L-1), the adhesion ability of the two kinds cells were tested bymodified MTT assay with FN; Transwell Chambers experimental method was usedfor evaluating the migration and invasion of this two kinds of cells; The expressionlevels of β-catenin, GSK-3β, MMP-2, MMP-9, E-cadherin and VEGF mRNA andprotein were detected by RT-PCR and Western Blot.Results：⑴Raji cells and JeKo-1cells were treated with FNC for24h, FNC couldremarkably inhibit the adhesion of them in dose-dependent manner.⑵Raji cells and JeKo-1cells were treated with FNC for24h, FNC couldremarkably inhibit the migration and invasion of them in dose-dependent manner.⑶In Raji cells and JeKo-1cells, the expressions of β-catenin, MMP-2,MMP-9, VEGF mRNA and protein decreased with the increasing dose of FNC, whilethe expressions of GSK-3β and E-cadherin increased.Conclusion：⑴FNC inhibits cell adhesion, migration and invasion in Raji cells and JeKo-1cells.⑵Down-regulation of β-catenin, up-regulation of GSK-3β and E-cadherin byacting on Wnt/β-catenin signaling pathway, resulting in decrease the expression ofMMP-2, MMP-9and VEGF, leads to the inhibition of cell invasion and metastasis.⑶FNC mayplay a role of resistance to non-Hodgkin’s lymphoma throughmultiple targets.