title: FNC, a novel nucleoside analogue, blocks invasion of aggressive non-Hodgkin lymphoma cell lines via inhibition of the Wnt/β-catenin signaling pathway.
abstract: Chemotherapy is the primary therapy for malignant lymphoma (ML). However, the clinical outcome is still far from satisfactory. Consequently, an understanding of the mechanism of modulating cancer cell invasion, migration and metastasis is important for the development of more effective chemotherapeutic agents. FNC, 2'- deoxy- 2' -β- fluoro -4'- azidocytidine, a novel cytidine analogue, has demonstrated significantly inhibitory effects on proliferation of several non-Hodgkin lymphoma (NHL) cell lines. A previous study indicated that FNC effectively inhibited the growth of Raji and JeKo-1 cells in dose-time dependent effects with IC50 values of 0.2μM and 0.097μM, respectively. This study was focused on investigating the anti-invasive properties of FNC on NHL cells and its potential mechanisms of action. Cell adhesion and transwell chamber assays were utilized to investigate the anti-invasive effects of FNC on Raji and JeKo-1 cells. Real-time PCR and Western blotting were employed to qualify the expression of β-catenin, the glycogen synthase kinase-3 beta (GSK-3β), E-cadherin vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). The results revealed that FNC remarkably inhibited the adhesion, migration and invasion of two human aggressive non-Hodgkin lymphoma cell lines in a dose dependent manner. Furthermore, β-catenin, MMP-2, MMP-9, VEGF mRNA and protein levels were decreased after FNC treatment, while GSK-3β and E-cadherin increased. Our studies thus provide evidence and a rationale that FNC may offer an effective chemotherapeutic agent by regulating the invasion and metastasis of aggressive non-Hodgkin lymphoma via inhibition of the Wnt/β-catenin signaling pathway.
authors.affiliation: Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China E-mail : changjunbiao@zzu.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Chen-Ping
authors.initials: CP
authors.lastname: Wang
authors.forename: Xi-Xi
authors.initials: XX
authors.lastname: Ding
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.forename: Fang
authors.initials: F
authors.lastname: Ma
authors.forename: Jin-Hua
authors.initials: JH
authors.lastname: Jiang
authors.forename: Qing-Duan
authors.initials: QD
authors.lastname: Wang
authors.forename: Jun-Biao
authors.initials: JB
authors.lastname: Chang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001386:Azides / Q000494:pharmacology*; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000096:biosynthesis / Q000235:genetics; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D012333:RNA, Messenger / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics; D051153:Wnt Proteins / Q000037:antagonists & inhibitors; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D001386:Azides; D015820:Cadherins; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051153:Wnt Proteins; D051176:beta Catenin; D003841:Deoxycytidine; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C540945:azvudine