全反式维甲酸对乳腺癌干细胞的抑制作用  

All-trans retinoic acid effectively inhibits breast cancer stem cells growth in vitro

作　　者：曾维根[1] 胡攀[1] 王佳妮[1] 刘仁斌[1] 

机构地区：[1]中山大学附属第三医院乳腺疾病诊治中心,广州510630

出　　处：《中华肿瘤杂志》2013年第2期89-93,共5页Chinese Journal of Oncology

基　　金：国家自然科学基金（30672410）;广东省自然科学基金（06104599）

摘　　要：目的研究全反式维甲酸（ATRA）对乳腺癌干细胞的抑制作用。方法采用CCK-8法检测ATRA对MCF-7和SK—BR-3细胞及其干细胞的抑制作用，并检测ATRA处理前后干细胞表型CD44^＋CD24^-的比例变化。利用球囊形成实验，研究ATRA对乳腺癌干细胞的自我更新能力的影响；将球囊贴壁培养，观察ATRA对干细胞分化的影响。结果ATRA能够有效的抑制MCF-7和SK-BR-3细胞及其干细胞，但干细胞对ATRA更加敏感。10^-6mol／LATRA对MCF-7细胞和干细胞的抑制率分别为（8．66±1．06）％和（21．09±3．25）％（P=0．004），对SK-BR-3细胞和干细胞的抑制率分别为（39．19±1．47）％和（51．22±2．80）％（P=0．005）。ATRA能有效地抑制干细胞的成球能力，破坏其自我更新能力。10^-6mol／LATRA处理后，MCF-7和SK—BR-3干细胞成球率分别为5．2％（5／96）和13．5％（13／96），而对照组分别为86．5％（83／96）和93．8％（90／96，均P〈0．001）。ATRA能促进CD44^＋CD24^-表型分化。10^-6mol／LATRA处理SK-BR-3干细胞后，CD44^＋CD24^-比例下降为（48．10±2．50）％，而对照组为（86．604-2．50）％（P〈0．001）。结论ATRA能有效地抑制乳腺癌细胞和干细胞，但是对干细胞更敏感；ATRA能破坏乳腺癌干细胞的自我更新能力，并促进其分化。Objective To detect the inhibitory effect of all-trans retinoic acid （ATRA） on breast cancer stem cells （CSCs＇）. Methods The inhibitory effect of ATRA on MCF-7 and SK-BR-3 cell lines was analyzed using a Cell Counting Kit-8 （CCK-8）. The proportion of CD44 ^± CD24 ^- tumor cells of the two cell lines were measured before and after the ATRA treatment, and the role of ATRA in the regulation of CSC self-renewing ability was evaluated with a tumor sphere assay. The tumor spheres were grown in an adherent cuhure to evaluate the ATRA-induced differentiation of breast cancer stem cells. Results ATRA effectively inhibited the unsorted cells and stem cells, but the CSCs were more sensitive to ATRA. At a concentration of 10-6 mol/L, the inhibitory rate of MCF-7 unsorted cells and stem cells were （8.66 ± 1.06）% and （21.09 ± 3.25） %, respectively （P = 0. 004 ）. For SK-BR-3 cells, the rates were （39. 19 ± I. 47） % and （51.22 ± 2.80）%, respectively （P =0. 005）. The self-renewing ability of the CSCs was impaired by ATRA at a concentration of 10^-6 mol/L. The rate of MCF-7 and SK-BR-3 stem cells to form tumor sphere was 5.2% （5/96） and 13.5% （13/96）, respectively. For the control group, it was 86. 5% （83/96） and 93.8% （90/96）, respectively （P 〈 0.001 ）. ATRA also promoted the CD44 ^＋CD24^- subpopulation to differentiate. SK-BR-3 stem cells were grown in an adherent culture. After using ATRA, the proportion of CD44 ^＋ CD24 ^- cells was （48.1 ±2.5）% and that of the control group was （86.6 ±2.5）% （P〈0.001）. Conclusions ATRA effectively inhibits breast NCSCs and CSCs, but CSCs are more sensitive to ATRA. ATRA impairs the self- renewing ability of CSCs and promotes CSCs to differentiate.

关 键 词：全反式维甲酸 乳腺肿瘤 肿瘤干细胞 细胞分化 

分 类 号：R737.9[医药卫生—肿瘤]