长程多柔比星化疗富集乳腺肿瘤干细胞  

Enrichment of breast cancer stem cells after prolonged and continuous chemotherapy with adriamycin

作　　者：郭崇勇[1] 李克[1] 周凌[2] 柯卫锋[1] 王建丰[1] 王瑞涛[1] 宋科瑛[1] 

机构地区：[1]上海交通大学附属第一人民医院普外科,上海200080 [2]上海市第一人民医院分院普外科,上海200081

出　　处：《肿瘤》2012年第1期27-31,共5页Tumor

摘　　要：目的:探讨长程多柔比星(adriamycin,ADR)作用乳腺癌细胞株MCF-7对富集肿瘤干细胞的可能性。方法:采用长程ADR诱导的方法建立ADR耐药细胞株MCF-7/ADR’。ALDEFLUOR法检测亲本MCF-7细胞及ADR耐药细胞MCF-7/ADR’中乙醛脱氢酶1(aldehyde dehydrogenase 1,ALDH1)阳性的肿瘤干细胞亚群的比例,然后采用无血清悬浮培养和裸鼠成瘤实验分别检测两者在体外形成干细胞微球体和体内成瘤能力的差异。结果:MCF-7和MCF-7/ADR’细胞中ALDH1+肿瘤干细胞亚群的比例分别为(0.82±0.77)%和(8.21±2.38)%,两者差异有统计学意义(P<0.05);两者经无血清悬浮培养形成干细胞微球体的比例分别为(2.17±0.70)%和(7.87±1.39)%,差异有统计学意义(P<0.05)。MCF-7/ADR’细胞在裸鼠体内的成瘤能力明显强于MCF-7细胞。结论:长程ADR作用MCF-7后可富集肿瘤干细胞。Objective： To investigate whether prolonged and continuous selection of cells for adriamycin （ADR） resistance can enrich cancer stem cells from MCF-7 breast cancer cells. Methods： The ADR-resistant MCF-7/ADR＇ cells were selected through prolonged and continuous chemotherapy with ADR. The percentage of aldehyde dehydrogenase 1 positive （ALDHI＋） cancer stem cells in cell line MCF-7/ ADR＇ and its parental cell line MCF-7 was examined by using ALDEFLUOR kit. The differences in abilities of ALDH1 ＋ cancer stem cells to form microspheres in vitro and to develop tumors in vivo were examined by serum-free suspension culture and xenotransplantation experiment in nude mice, respectively. Results： Statistically significant difference was observed in the percentage of ALDH1＋ cells between MCF-7 cells and MCF-7/ADR＇ cells [（0.82±0.77）% vs （8.21±2.38）%; P〈0.05]. The result of serum-free suspension culture showed that the ability to form microspheres was more significantly increased in MCF-7/ADR＇ cells than that in MCF-7 cells [（7.87±1.39）% vs （2.1 7±0.70）%; P〈0.05]. The tumorigenic ability of MCF-7/ ADR＇ cells was stronger than that of MCF-7 cells in nude mice. Conclusion： The Prolonged and continuous chemotherapy with ADR may enrich breast cancer stem cells from MCF-7 cells.

关 键 词：乳腺肿瘤 肿瘤干细胞 抗药性 肿瘤 小鼠 裸 

分 类 号：R737.9[医药卫生—肿瘤]