Study on the Anti-tumor Effect and Mechanism of COX-2 Inhibitor in ECa109 Cells through MMP-14 Pathway

ZeXin Hou^1#, Jun Li^1#, SiYuan Li^2#, QingQing Du^1#, LiMin Song¹, ZhiWei Xiao^3#, RuJun Lin¹, MengYao Zhao¹, XueJiao Ji¹

¹Department of Endocrinology and Metabolism, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang 832002, China - ²Medical College, Shihezi University, Shihezi 832002, China - ³Unit 69296 of the Xinjiang Military Command, Kashgar 844000, China

Objective: Esophageal squamous cell carcinoma (ESCC) refers to the commonest pathological type of esophageal cancer, but it is difficult to find ESCC in the early stage, together with unfavourable prognosis. Reserarch on the relationship between tumor and cyclooxygenase-2 (COX-2) is a current research hotspot, but there are few studies on the relationship between celecoxib (COX-2 inhibitor) and ESCC. Our objective was to analyze the function of celecoxib in the cell proliferation, invasion and apoptosis of esophageal cancer ECa109 cells, and the possible mechanism of celecoxib anti-esophageal cancer is also discussed.

Methods: ECa109 cells can be treated with different concentrations (20, 60, 100μmol /L) of celecoxib for different times (24h, 48h, 72h). MTT assay can be used for detecting cell proliferation, flow cytometry (FCM) for detecting cell apoptosis, Transwell invasion test for detecting cell invasion, the expression of COX-2 and MMP-14 protein was detected by enzyme-linked immunosorbent assay, and the correlation between COX-2 and MMP-14 was analyzed by Pearson method.

Results: MTT results showed that celecoxib inhibition of ECa109 proliferation was time-dose dependent compared to the control group. Transwell invasion assay results showed that celecoxib reduced invasion of ECa109 cells in a concentration-dependent manner compared to the control group. Flow cytometry showed that celecoxib promoted apoptosis of ECa109 cells in a concentration-dependent manner.

Celecoxib down-regulated COX-2 and MMP-14 protein expression in a concentration-dependent manner. MMP-14 had a positive relation with COX-2 expression.

Conclusion: Celecoxib may inhibit the expression of COX-2, down-regulate the expression of MMP-14, weaken the proliferation and invasion of esophageal cancer Eca109 cells, and promote the apoptosis, thus playing a role in anti-esophageal cancer.