结肠癌尿激酶分子系统调节作用的研究

目的研究转化生长因子β_1（TGF-β_1）和丁酸钠对结肠癌LoVo细胞的增殖、尿激酶型纤溶酶原激活剂（UPA）和纤溶酶原激活物抑制剂（PAI-1）的调节作用,探讨肿瘤浸润转移的机制。方法选择体外培养的LoVo细胞,分为对照组、TGF-β_1组、丁酸钠组、TGF-β_1＋丁酸钠组,分别在无血清培养条件下处理细胞,以~3H-TdR掺入法观察TGF-β_1和丁酸钠对细胞增殖的影响,并应用纤溶酶特异的发色底物法和酶联免疫测定法分别测定它们对结肠癌LoVo细胞UPA和PAI-1的调节作用,并同时观察不同条件处理后细胞形态和黏附度的变化。结果 TGF-β_1对LoVo细胞增殖无影响,但可增加UPA和PAI-1的含量。丁酸钠抑制细胞增殖和UPA活性,而不影响PAI-1的水平。结论 TGF-β_1通过提高UPA和PAI-1的水平促进肿瘤细胞的侵袭和转移。丁酸钠则可抑制细胞增殖和侵袭而阻止肿瘤发展。

Modulation of Urokinase System in Colon Cancer Cell Line

Objective To study the effects of transforming growth factor B,（TGF-β_1） and sodium butyrate on cell proliferation and urokinase plasminogen activator system in colon cancer cell line,LoVo,and to explore the mechanism of invasion and metastasis of tumor.Methods In vitro,LoVo cells were divided into control group,TGF-β_1 group,sodium butyrate group,TGF-B,and sodium butyrate group.Effects of TGF-β_1 and sodium butyrate on proliferation of LoVo cell line in serumfree culture medium were observed by means of meauring the incorporation of ~3H-thymidine,and the modulation of TGF-β_1 and sodium butyrate on urokinase plasminogen activator（UPA） and plasminogen activator inhibitor-1（PAI-1） were observed by determining the chromogenic substrate and using the ELISA kit of PAI-1.The effect of TGF-β_1 and sodium butyrate on cell detachment was also studied.Results TGF-β_1 had no effect on cell proliferation but increased UPA activity and PAI-1 level,sodium butyrate inhibited both cell proliferation and UPA activity but had no effect on PAI-1 level.Conclusion TGF-β_1 may promote invasion and metastasis of tumor cells by increasing UPA activity and PAI-1 level,and that sodium butyrate may prevent tumor development by inhibiting both cell proliferation and invasion.