CXCR4 silencing inhibits invasion and migration of human laryngeal cancer Hep-2 cells.
CXCR4 has been reported in various types of human cancer, which is associated with cancer progression and metastasis. However, the investigation of CXCR4 in laryngeal cancer is extremely rare. In the present study, we used lentivirus-mediated shRNA targeting CXCR4 to silenced CXCR4 expression in Hep-2 cells and evaluated the effect of long-term suppression of CXCR4 on Hep-2 growth and metastasis. The Cell proliferation was analyzed by MTS assay, and the invasion and metastasis potentials were analyzed using wound healing and transwell assays, respectively. Our results showed that lentivirus-mediated shRNA effectively infected Hep-2 cells and suppressed CXCR4 expression, and inhibited cell growth of Hep-2 cells. Cell invasion and apoptosis were decreased concomitantly with the reduction in CXCR4 protein expression. Further analysis revealed that CXCR4 silencing caused the reducion of CXCR4, CXCL12, TIMP2, VEGF and MMP9, and the phosphorylation levels of IκB, AKT and MAPK, and also decreased the activity of NF-κB. These results suggested that knockdown of CXCR4 inhibits the invasion and metastasis of Hep-2 through PI3K/AKT and MAPK signaling pathways, by decreasing NF-κB activities to down-regulate VEGF, TIMP-2 and MMP-9 expression. These data demonstrate that the inhibition of CXCR4 may be an effective interventional therapeutic strategy in laryngeal cancer.
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy Tianjin 300060, China ; Department of Otorhinolaryngology, The Second Hospital of Tianjing Medical University Tianjin 300211, China.
Juntao
J
Niu
Department of Otorhinolaryngology, The Second Hospital of Tianjing Medical University Tianjin 300211, China.
Yongwang
Y
Huang
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy Tianjin 300060, China.
Lun
L
Zhang
D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000235:genetics*; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000235:genetics; D014162:Transfection
C527276:CXCR4 protein, human; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4
CXCR4; invasion; laryngeal cancer