5-Fu诱导人大肠癌SW480细胞株耐药与自噬活性的变化

Relationship of the Autophagy and Resistant Induction of Colorectal Cancer Cell SW480 to 5-Fu in Vitro

目的:观察结直肠癌细胞产生5-Fu耐药过程中自噬水平的变化,探讨自噬活性变化在结直肠癌细胞耐药形成过程中的作用。方法:用浓度递增筛选法诱导耐受不同5-Fu浓度的耐药SW480细胞株,MDC染色和透射电镜观察SW480细胞内的自噬泡数量,CCK-8法检测细胞活力。结果:成功的诱导出三个水平的耐药细胞株;随着耐药浓度的升高,结直肠癌细胞的自噬水平逐渐增高,高水平耐药细胞株内自噬泡的数量较低水平耐药及正常SW480细胞显著增高(P<0.05),而5-Fu对其抑制率却相应的降低。结论:细胞自噬活性的增加参与了结直肠癌细胞对5-Fu的耐药过程。

Objective To investigate the role of autophagy activity in the formation of durg resistance to 5-Fu, we made colorectal cancer cell SW480 resistant to 5-Fu in vitro and tried to explore the relationship be- tween autophagic levels and drug resistance. Methods Stepwise 5-Fu selection was used to establish the 5-Fu resistant subliMes. Autophagic vacuoles in cells were observed by means of transmission electron microsco- py and monodansylcadaverine （MDC）. Cell proliferation inhibition rate were measured by CCK8. Results The 5-Fu resistant cell lines we established can be resistant to 25 Ixg, 50 p^g, i00 lxg/L 5-Fu. the numbers of autoph- agic vacuoles in the 5-Fu resistant cell lines were obviously more than those in normal SW480cells（P 〈 0.05）, gradually increasing with the levels of resistance, but the level of cell proliferation inhibition rate was markedly lower in the 5-Fu resistant cell lines than those in control ceils. Conclusion 5-Fu resistant SW480 cells have greater autophagy and autophagy is involved in 5-Fu resistance.