The role of COX-2 in the proliferation and invasion of oral squamous cell carcinoma

doi:10.11958/20253464

Abstract

Abstract:

Objective To explore the role of cyclooxygenase-2 (COX-2) in the proliferation, migration, invasion and tumorigenesis in vivo of oral squamous cell carcinoma (OSCC) cells. Methods Tissue samples, including five cases of normal oral mucosa and five cases of OSCC, were collected postoperatively from the Department of Stomatology, Hainan Cancer Hospital. Immunohistochemistry was performed to detect the expression of COX-2 in both groups. Celecoxib and COX-2 shRNA were used to inhibit the expression of COX-2 in SCC9 cells, and the inhibition efficiency was verified by Western blot assay. The proliferation ability of cells was evaluated by CCK-8 and colony formation assays. The migration and invasion abilities of cells were detected by scratch and invasion assays. A subcutaneous xenograft tumor model of SCC9 cells in nude mice was established to observe the effect of COX-2 silencing on tumor growth. Results Immunohistochemistry showed that COX-2 was mostly negative or weakly positive in normal oral mucosa tissue, but strongly positive in OSCC tissue. Compared with the control group, both Celecoxib treatment and COX-2 shRNA transfection could down-regulate the expression of COX-2 protein in SCC9 cells (P<0.05), and reduce the OD₄₅₀ value of cells, the number of clones, the scratch healing rate and the number of transmembrane cells. The xenograft tumor experiment in nude mice showed that with the extension of tumor formation time, the tumor volume in the COX-2 silencing group decreased, and the final measured body weight was lower than that in the empty vector group (P<0.05). Conclusion COX-2 is highly expressed in OSCC and participates in the proliferation, migration, invasion and in vivo growth of tumors. The inhibition of COX-2 can weaken the malignant biological behavior of OSCC cells.

Key words: mouth neoplasms, carcinoma, squamous cell, cyclooxygenase 2, cell proliferation, cell movement

CLC Number:

R739.8

Figures/Tables 8

References 20

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组别	24 h	48 h	72 h	96 h
Control组	0.35±0.01	0.59±0.07	0.84±0.02	1.08±0.03
Empty Vector组	0.34±0.02	0.57±0.02	0.82±0.03	1.07±0.00
Celecoxib 20 μg/L组	0.35±0.05	0.45±0.00^ab	0.70±0.02^ab	0.83±0.01^ab
Celecoxib 50 μg/L组	0.31±0.03	0.46±0.03^ab	0.56±0.01^abc	0.72±0.03^abc
COX-2 shRNA组	0.32±0.05	0.46±0.04^ab	0.64±0.04^abcd	0.73±0.02^abc
F	0.732	8.903^＊＊	7.301^＊＊	14.554^＊＊

组别	24 h	48 h	72 h	96 h
Control组	0.35±0.01	0.59±0.07	0.84±0.02	1.08±0.03
Empty Vector组	0.34±0.02	0.57±0.02	0.82±0.03	1.07±0.00
Celecoxib 20 μg/L组	0.35±0.05	0.45±0.00^ab	0.70±0.02^ab	0.83±0.01^ab
Celecoxib 50 μg/L组	0.31±0.03	0.46±0.03^ab	0.56±0.01^abc	0.72±0.03^abc
COX-2 shRNA组	0.32±0.05	0.46±0.04^ab	0.64±0.04^abcd	0.73±0.02^abc
F	0.732	8.903^＊＊	7.301^＊＊	14.554^＊＊

组别	克隆数/个	划痕愈合率/%	穿膜细胞数/个
Control组	223.09±10.94	64.51±13.09	126.33±11.28
Celecoxib 20 μg/L组	145.04±5.06^a	46.24±6.13^a	82.64±6.15^a
Celecoxib 50 μg/L组	26.99±13.66^ab	27.41±3.19^ab	54.18±5.02^ab
Empty Vector组	197.43±2.17	66.55±3.90	121.47±9.36
COX-2 shRNA组	45.55±5.55^ac	33.96±2.77^ac	49.37±4.88^ac
F	318.073^＊＊	19.218^＊＊	65.220^＊＊

组别	克隆数/个	划痕愈合率/%	穿膜细胞数/个
Control组	223.09±10.94	64.51±13.09	126.33±11.28
Celecoxib 20 μg/L组	145.04±5.06^a	46.24±6.13^a	82.64±6.15^a
Celecoxib 50 μg/L组	26.99±13.66^ab	27.41±3.19^ab	54.18±5.02^ab
Empty Vector组	197.43±2.17	66.55±3.90	121.47±9.36
COX-2 shRNA组	45.55±5.55^ac	33.96±2.77^ac	49.37±4.88^ac
F	318.073^＊＊	19.218^＊＊	65.220^＊＊

组别	0周	1周	2周	3周	4周	5周	6周
Empty Vector组	52.18±9.24	130.46±18.59	289.74±35.42	559.87±62.28	919.65±85.73	1 270.52±110.36	1 519.74±135.82
COX-2shRNA组	48.92±8.26	95.38±15.63	184.56±28.19	329.42±40.74	520.28±55.42	689.84±70.58	610.29±58.46
t	0.588	3.230^＊	5.195^＊＊	12.401^＊＊	16.230^＊＊	17.816^＊＊	31.632^＊＊