Effect of AA861 combined with celecoxib on metastatic colon carcinoma cell

Abstract

Objective To investigate the effects of cyclooxygenase-2 (COX-2) selective inhibitor combined with 5-lipoxygenase (5-LOX) inhibitor docebenone (AA861) on cell proliferation and migration of human colon cancer cell line HT-29. Methods Cultured in vitro of HT-29 cells in high metastatic colon cancer, A A861 and celecoxib on colon cancer cell drugs for 48 h, the cell proliferation was assayed by MTT; the migration of cell was detected by Transwell; immunofluorescence staining of intracellular changes in ICAM-1 protein, RT-PCR detect the gene expression of ICAM-1 and VEGF. Results MTT and Transwell experiments showed that the inhibition on celecoxib and AA861 on colon cancer was dose-dependent and time-dependent. And the inhibition of AA861 and celecoxib 100 μmol/L alone on colon cancer cells proliferation were 43.2 % and 42.8%, and when the two drugs 100 μmol/L combined on colon cancer cells the inhibition was 53.8%, and the difference between alone group and combined group was statistical (P ＜0.001). The inhibition of AA861 and celecoxib 100 μmol/L alone on colon cancer cells migration were 32.0 % and 29.3%, and when the two drugs 100 μ,mol/L combined on colon cancer cells the inhibition is 57.8 %, and the difference of between alone group and combined group was statistical (P ＜0.001). Immunefluorescence staining and RT-PCR results suggested that the two drugs can inhibit ICAM-1 and VEGF protein and gene expression, and when the two drugs combined, a stronger inhibition effect appeared than used alone (P＜0.001). Conclusion Low-dose celecoxib and AA861 combined has a synergistic inhibited effect on colon cancer cells invasion and metastasis, and the mechanism relates with the VEGF and ICAM-1 expression. Key words: Neoplasms, experimental; Colonic neoplasms; Drug therapy, combination; Neoplasms metastasis