Effects Of Nimesulide Cyclooxygenase-2 Selected Inhibitor On Invasion And Metastasis Activity Of Human Colon Cancer Cells

Objective: Cyclooxygenase-2 (COX-2), the rate-limiting enzyme that converts arachidonic acid to prostaglandin, have two isoenzymes, COX-1 and COX-2. Epidemiologic studies have shown an inverse correlation between the incidence of colon cancer and the usage of nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit prostaglandin synthesis. The NSAIDs target cyclooxygenases (COX). Studies show there is a close relationship between the overexpression level of COX-2 and the occurrence, progression, metastasis and recurrence of colon cancer, but the specific mechanism is unknown. It is necessary to investigate the mechanism of invasion and metastasis and prevention from forming of colon cancer. Nimesulide, a kind of cyclooxygenase-2 selected inhibitor drugs, belong to methylsulfonyl benzenamine, is supposed to inhibit the expression of COX-2 selectively, inverse the metastasis and relapse of colon cancer. This study was designed to explore effects of nimesulide cyclooxygenase-2 selected inhibitor on invasion and metastasis activity of human colon cancer cells and to define the clinical chemoprophylaxis potential of nimesulide in human colon cancer.Methods: Two colon cancer cell lines were cultured and treated with nimesulide and the antitumor activity was detected by MTT assay. Distribution of cell cycle was assessed by flow cytometry. Immunohistochemical Streptavidin/Peroxidase method was used to assess the expression of E-cadherin of the treated cells. Total RNA was extracted from the treated cells and PT-PCR was used to determine the effect of the treatment on the expression of ICAM-1 mRNA. Modified quantitative zymography was used to confirm the expression of MMP-2 of the treated cells.Results: Nimesulide inhibited tumor cells proliferation in a time and dose-dependent fashion, and caused cancer cells' G0/G1 arrest, the inhibitary effect on HT-29 cells were stronger than on HCT-116 cells. Nimesulide induced an increased expression of E-cadherin in HT-29 cells but not HCT-116 cells. Exposed to Nimesulide, the expression level ofICAM-1 mRNA is decreased in HT-29 cells, but isn't changed in HCT-116 cells. Nimesulide reduced the MMP-2's expression of HT-29 cells, whereas the expression level of HCT-116 cells was unchanged.Conclusion: Treatment with nimesulide could inhibit the expression of COX-2 selectively, suppress cancer cells' proliferation and then influence the expression of E-cadherin ICAM-1 and MMPs, lead to the depression of metastasis and invasion activity of primary colon cancer.