[In vitro investigation on the mechanism of cyclooxygenase-2 upregulation induced by spleen tyrosine kinase-nuclear factor κB signaling in cancer pain caused by oral cancer-associated macrophage].
OBJECTIVE
This study explores the mechanism of cyclooxygenase-2 (COX-2) upregulation in oral cancers associated with macrophage by using molecular biology techniques and primary culture of murine macrophage.


METHODS
Murine macrophage was induced by macrophage colony-stimulating factor (M-CSF) and Cal27 conditional medium (CM). Purity of the macrophage was detected through CD68 immunofluorescence staining. Inhibitors of spleen tyrosine kinase (Syk) and nuclear factor κB (NFκB) were used to inhibit these pathways. In addition, real-time polymerase chain reaction and Western blot analysis were used to detect alterations in COX-2 and pathway-related proteins.


RESULTS
All of the induced cells specifically expressed CD68. Cal27 CM could significantly induce COX-2 expression (P<0.001). Moreover, inhibition of Syk pathway attenuated NFκB-P65 phosphorylation and reduced COX-2 expression (P<0.01), and inhibition of NFκB pathway exerted no effects on Syk phosphorylation but significantly inhibited COX-2 upregulation (P<0.01).


CONCLUSIONS
Syk-NFκB is responsible for COX-2 overexpression in oral cancer associated with macrophages. Targeting this pathway is possibly a new approach to control oral cancer-related pain. .
State Key Laboratory of Oral Diseases, Dept. of Dental Anesthesia, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
Lin
L
Jie
State Key Laboratory of Oral Diseases, Dept. of Dental Anesthesia, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
Wang
W
Miao
State Key Laboratory of Oral Diseases, Dept. of Dental Anesthesia, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
Ji
J
Yang
State Key Laboratory of Oral Diseases, Dept. of Dental Anesthesia, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
Liu
L
Le
State Key Laboratory of Oral Diseases, Dept. of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
Gao
G
Pan
State Key Laboratory of Oral Diseases, Dept. of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
Li
L
Chunjie
D000818:Animals; D000072716:Cancer Pain; D051546:Cyclooxygenase 2; D016173:Macrophage Colony-Stimulating Factor; D008264:Macrophages; D051379:Mice; D009062:Mouth Neoplasms; D016328:NF-kappa B; D010766:Phosphorylation; D015398:Signal Transduction; D013154:Spleen; D000072377:Syk Kinase; D015854:Up-Regulation
D016328:NF-kappa B; D016173:Macrophage Colony-Stimulating Factor; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D000072377:Syk Kinase; C000606897:Syk protein, mouse
cancer pain; cyclooxygenase-2; macrophage; mouth neoplasm