盐霉素和盐霉素钠对人乳腺癌干细胞和乳腺癌细胞体外细胞毒作用的比较

doi:10.5246/jcps.2011.04.046

盐霉素和盐霉素钠对人乳腺癌干细胞和乳腺癌细胞体外细胞毒作用的比较

张杨, 王学清, 王坚成, 张烜, 张强^*

北京大学医学部天然药物及仿生药物国家重点实验室; 药学院药剂学系, 北京 100191

收稿日期:2011-03-17 修回日期:2011-05-10 出版日期:2011-07-01 发布日期:2011-07-01
通讯作者: 张强*

A comparison study of the cytotoxicity of salinomycin and salinomycin sodium toward human breast cancer stem cells as well as breast cancer cells

Yang Zhang, Xue-Qing Wang, Jian-Cheng Wang, Xuan Zhang, Qiang Zhang^*

State Key Laboratory of Natural and Biomimetic Drugs; Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2011-03-17 Revised:2011-05-10 Online:2011-07-01 Published:2011-07-01
Contact: Qiang Zhang*

摘要/Abstract

摘要： 盐霉素是一种从白色链丝菌培养物中分离提取的聚醚类离子载体型抗生素, 它广泛应用于畜禽类动物鸡球虫病的防治, 并且还能作为饲料添加剂以促进畜禽的生长。最近新发现盐霉素具有特异性抑制肿瘤干细胞的作用。目前盐霉素钠的价格只是盐霉素的十分之一, 但两者在抑制肿瘤细胞和肿瘤干细胞方面的异同却未见文献报导。本研究以人乳腺癌细胞MCF-7及其干细胞为模型, 通过SRB实验对盐霉素及其钠盐的细胞毒性进行了评价和比较。首先, 通过流式细胞仪从MCF-7细胞中分选得到了SP细胞; 然后用乳腺癌干细胞表面特异性标志物CD44⁺/CD24^-对SP细胞进行了鉴定; 最后, 分别测定了盐霉素和盐霉素钠对分选得到的肿瘤干细胞和肿瘤细胞的体外生长抑制率。结果表明, 与乳腺癌细胞相比较, 盐霉素和盐霉素钠对肿瘤干细胞均表现出了更强的抑制作用; 在同样的给药浓度下, 盐霉素和盐霉素钠对肿瘤细胞和肿瘤干细胞的抑制作用未表现出明显的差异。本研究结果提示, 在抑制肿瘤干细胞的相关研究中, 可以用盐霉素钠替代盐霉素而不会影响抑制效果。

关键词: 盐霉素, 盐霉素钠, 肿瘤干细胞, 人乳腺癌细胞MCF-7

Abstract: Salinomycin (SAL), a polyether antibiotic isolated from Streptomyces albus, is widely used as an anticoccidial drug in poultry and other livestock and is furthermore fed to ruminescent animals to improve nutrient absorption and feed efficiency. It has recently been shown to act as a specific inhibitor of cancer stem cells. At present, the price of salinomycin sodium (SAL-Na) is 10 fold lower than that of salinomycin, however, there is no report about the comparison of the inhibitory effects of SAL and SAL-Na on cancer stem cells as well as cancer cells. In the present study, side population cells (SP cells) and non-SP cells (NSP cells) sorted from human breast cancer cell line MCF-7 were chosen as the models of cancer stem cells and cancer cells, respectively. SRB assay was performed to compare the cytotoxicity of SAL and SAL-Na. First of all, SP cells were sorted from MCF-7 cells via FACSDiva flow cytometry. Secondly, the sorted SP cells were identified with the surface makers (CD44⁺/CD24^-) of breast cancer stem cells. Finally, the inhibitory effects of SAL and SAL-Na were evaluated on the sorted SP cells and NSP cells. Results showed that, as compared to breast cancer cells, the inhibitory effect of free SAL or free SAL-Na was more potent in breast cancer stem cells. Furthermore, the inhibitory effects of free SAL and free SAL-Na had no significant difference for the SP cells as well as the NSP cells when they were in the same concentration. Thus, it suggested that salinomycin sodium should be considered as a potential candidate to take the place of salinomycin in cancer stem cells research, due to their similar inhibitory effects on cancer stem cells.

Key words: Salinomycin, Salinomycin sodium, Cancer stem cells, Human breast cancer cell line MCF-7

中图分类号:

Supporting:

Foundation items: National Basic Research Program of China (Grant No. 2009CB930300), State Key Projects (Grant No. 2009ZX09310-001) and the 863 Project (Grant No. 2007AA021811).

^*Corresponding author. Tel./Fax: 86-10-82802791; E-mail: zqdodo@bjmu.edu.cn

张杨, 王学清, 王坚成, 张烜, 张强^*. 盐霉素和盐霉素钠对人乳腺癌干细胞和乳腺癌细胞体外细胞毒作用的比较[J]. , DOI: 10.5246/jcps.2011.04.046.

Yang Zhang, Xue-Qing Wang, Jian-Cheng Wang, Xuan Zhang, Qiang Zhang^*. A comparison study of the cytotoxicity of salinomycin and salinomycin sodium toward human breast cancer stem cells as well as breast cancer cells[J]. , DOI: 10.5246/jcps.2011.04.046.

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