盐霉素对结肠癌干细胞特性的抑制作用  

Inhibition of Salinomycin on the characteristics of colon cancer stem cell

作　　者：孙秀梅[1] 高峰[2] 刘子凤[3] 

机构地区：[1]潍坊医学院临床医院肿瘤科,山东潍坊261000 [2]潍坊市人民医院肛肠外科,山东潍坊261000 [3]秦皇岛市第三医院肿瘤科,河北秦皇岛066000

出　　处：《山东大学学报（医学版）》2013年第9期40-44,共5页Journal of Shandong University:Health Sciences

摘　　要：目的探讨盐霉素对结肠癌干细胞(cCSC)的作用。方法通过无血清培养基(SFM)成球法筛选cCSC。检测盐霉素对cCSC的靶向性,并进一步研究盐霉素对cCSC的增殖能力、耐药性、克隆球形成能力、干细胞相关蛋白表达水平的作用。结果通过SFM成球法成功筛选出了cCSC,建立了理想的cCSC模型,cCSC对盐霉素的敏感性是HCT116+/+细胞的3倍。经盐霉素处理后,cCSC倍增时间从(1.21±0.15)d延长到了(1.54±0.04)d;对氟尿嘧啶(5-FU)的IC50从(40.21±3.02)μmol/L降到了(20.28±2.15)μmol/L,对奥沙利铂的IC50从(14.23±1.08)μmol/L降到(7.64±0.53)μmol/L;克隆球形成率由从(0.42±0.01)%下降到了(0.08±0.01)%;干细胞相关蛋白ABCG2、SOX2和OCT4表达水平明显降低。结论盐霉素对cCSC具有明显的靶向性,明显抑制了cCSC的增殖能力、耐药性、克隆球形成能力及干细胞相关蛋白的表达,为cCSC治疗提供了新的理论基础。Objective To investigate the impacts of Salinomycin on colon cancer stem cell （cCSC）. Methods The cCSC was screened by culturing the clone spheres in Serum Free Medium （SFM）. Further, we detected the targeting of Salinomycin to cCSC and studied the impacts of Salinomycin on the characteristics of cCSC including proliferation abili- ty, drug resistence, clone sphere forming ability, expression level of stem cell proteins. Results We acquired cCSC successfully by sphere culturing in SFM and established the ideal cCSC model. The cCSC showed triple sensitivity to Salinomycin than HCT116 -/- cell. After treatment by Salinomycin, the double time of cCSC increased from （1.21 x 0.15） days to （1.54 ± 0.04） days; the IC50 to 5-FU declined from （40.21 ± 3.02） umol/L to （20.28 ± 2. 15 ） umol/L, and the IC50 to oxaliplatin declined from （ 14.23 ± 1.08） umol/L to （7.64±0.53） /xmol/L; the clone sphere forming rate declined from （0.42 ± 0.01 ） % to （0.08 ± 0.01 ） % , and the expression level of ABCG2, SOX2 and OCT4 also declined significantly. Conclusion Salinomycin possesses significant targeting to cCSC, and can inhib- it the proliferation ability, drug resistence, clone sphere forming ability, expression level of stem cell proteins of cCSC. This provides new theory basis for cCSC therapy.

关 键 词：盐霉素 结肠癌干细胞 增殖 耐药 克隆球 

分 类 号：R735.35[医药卫生—肿瘤]