塞来昔布抑制骨肉瘤细胞黏附侵袭及其机制

Inhibitory effects of celecoxib on adhesion and invasion of osteosarcoma cell lines and the mechanisms

目的 观察环氧合酶2（COX-2）抑制剂塞来昔布对骨肉瘤MG-63和U2-OS细胞增殖、黏附和侵袭的抑制作用,探讨其分子机制.方法 采用噻唑蓝（MTF）比色法、黏附实验、侵袭实验、流式细胞术和Western blot研究25、50、100 μmol/L 3种浓度塞来昔布对两种细胞株增殖、黏附、侵袭能力及CD44和基质金属酶（MMP）-9表达的影响.结果 3种浓度的塞来昔布作用48 h后MG-63细胞增殖抑制率分别为9.35%、42.68%、60.29%（P＜0.05）,对U2-OS细胞的抑制率分别为2.59%、8.95%、29.36%（P＜0.05）.对MG-63的黏附抑制率分别为8.6%、21. 5%、52.8%（P＜0.05） 对U2-OS的黏附抑制率分别为1.6%、3.8%、19.0%（P＜0.05） 对两种骨肉瘤细胞的侵袭能力、CD44和MMP-9的表达均有抑制作用,对高表达COX-2的MG-63的抑制效应更加显著.结论 塞来昔布可抑制骨肉瘤细胞的增殖、黏附和侵袭,这种作用与下调CD44和MMP-9的表达有关,此种效应具有COX-2依耐性.

Objective To evaluate the effects of cyclooxygenase-2 （COX-2） inhibitor Celecoxib on the proliferation, adhesion and invasion of MG-63 and U2-OS osteosarcoma cell lines, and explore the molecular mechanisms. Methods Methyl thiazol tetrazolium （MTT） assay, adhesive assay and Transwell chamber in vitro invasion assay were employed to examine the change of the proliferation, adhesion and invasion ability of the cell lines which treated by different concentrations （25, 50, 100 μmol/L） of celecoxib for 24 h.Flow cytometry and Western blotting were used to detect the change of CD44 and matrix metalloproteinase （MMP）-9 expression after the treatment. Results The proliferation inhibition rate of the three concentrations of celecoxib on MG-63 cell line was 9. 35%, 42. 68%, 60. 29% （P 〈0. 05） respectively, on U2-0S cell line was 2. 59%, 8. 95%, 29. 36% （P 〈0. 05） respectively the adhesive inhibition rate on MG-63 cell line was 8.6%, 21.5%, 52.8% （P〈0.05） respectively, on U2-OS was 1.6%, 3.8%, 19.0% （P〈0. 05） respectively. The invasion ability and the expression of CD44 and MMP-9 in MG-63 and U2-OS cells were inhibited by celecoxib, but the inhibition effect was more obvious in MG-63 which expressed higher COX-2. Conclusion The selective COX-2 inhibitor celecoxib can inhibit the proliferation, adhesion and invasion of human osteosarcoma cell lines through downregulating the level of CD44 and MMP-9, which was COX-2-dependent.