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山东大学学报(医学版) ›› 2013, Vol. 51 ›› Issue (9): 40-44.

• 基础医学 • 上一篇    下一篇

盐霉素对结肠癌干细胞特性的抑制作用

孙秀梅1,高峰2,刘子凤3   

  1. 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
  • 收稿日期:2013-03-01 出版日期:2013-09-10 发布日期:2013-09-10
  • 通讯作者: 高峰,E-mail: gaofeng_@163.com

Inhibition of Salinomycin on the characteristics of colon cancer stem cell

SUN Xiu-mei1, GAO Feng2, LIU Zi-feng3   

  1. 1. Oncology Department, Affiliated Hospital of Weifang Medical University, Weifang 261000, Shandong, China;
     2. Department of Anus & Intestine Surgery, Weifang People′s Hospital,Weifang 261000, Shandong, China;
    3. Oncology Department, the Third Hospital of Qinhuangdao City, Qinhuangdao 066000, Hebei, China
  • Received:2013-03-01 Online:2013-09-10 Published:2013-09-10

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。

关键词: 盐霉素;结肠癌干细胞;增殖;耐药;克隆球

Abstract:

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 ability, 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±0.15) days to (1.54±0.04) days; the IC50 to 5-FU declined from (40.21±3.02) μmol/L to (20.28±2.15) μmol/L, and the IC50 to oxaliplatin declined from (14.23±1.08) μmol/L to (7.64±0.53) μmol/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 inhibit 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.

Key words: Salinomycin; Colon cancer stem cell; Proliferation; Drug resistence; Clone sphere

中图分类号: 

  • R735.35
[1] 褚倩倩1,许刚2,任桂杰1,徐霞1,胡中一1,刘永青1,苑辉卿1,田克立1. 过氧化物酶体增殖物激活受体γ激动剂对增强人结肠癌化疗敏感性的作用[J]. 山东大学学报(医学版), 2012, 50(1): 66-71.
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