Salinomycin Selectively Targets 'CD133+' Cell Subpopulations and Decreases Malignant Traits in Colorectal Cancer Lines

被引:112
作者
Dong, Tao-Tao [1 ,2 ,3 ]
Zhou, Hou-Min [1 ,2 ,3 ]
Wang, Lin-Lin [4 ]
Feng, Bo [1 ,2 ,3 ]
Lv, Bo [1 ,2 ,3 ]
Zheng, Min-Hua [1 ,2 ,3 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Surg, Shanghai 200030, Peoples R China
[2] Shanghai Inst Digest Surg, Shanghai, Peoples R China
[3] Shanghai Minimally Invas Surg Ctr, Shanghai, Peoples R China
[4] Shanghai Jiao Tong Univ, Sch Med, Shanghai 200030, Peoples R China
关键词
TUMOR-INITIATING CELLS; STEM-CELLS; COLON-CANCER; MESENCHYMAL TRANSITION; HEMATOPOIETIC STEM; RESISTANCE; RADIORESISTANCE; ANTIGEN; PLASMA;
D O I
10.1245/s10434-011-1561-2
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Cancer stem-like cells (CSCs) in colorectal cancers (CRC) may account for the failure of treatments because they are resistant to many current anticancer therapies. Salinomycin, a potassium ionophore, was recently identified as a selective inhibitor of breast CSCs. The human CRC cell lines HT29 and SW480 were treated with salinomycin and oxaliplatin. Cell viability was determined with cell counting kit 8. Fraction of CD133+ cell subpopulations was assessed by Flow Cytometric analysis. Clonogenecity and migration were determined with soft agar and Boyden chamber assays. Molecular changes were assessed by immunofluorescence staining, RT-PCR, and Western blot analysis. We report that salinomycin reduces the proportion of CD133+ subpopulations in human CRC HT29 and SW480 cells. Furthermore, salinomycin treatment decreases colony-forming ability and cell motility in HT29 cells. Moreover, salinomycin downregulates the expression of vimentin and induces the E-cadherin expression in HT29 cells. This study demonstrates the ability of salinomycin to selectively target "CD133+" cell subpopulations and decrease the malignant traits in colorectal cancer lines.
引用
收藏
页码:1797 / 1804
页数:8
相关论文
共 35 条
[1]
Tumour CD133 mRNA expression and clinical outcome in surgically resected colorectal cancer patients [J].
Artells, R. ;
Moreno, I. ;
Diaz, T. ;
Martinez, F. ;
Gel, B. ;
Navarro, A. ;
Ibeas, R. ;
Moreno, J. ;
Monzo, M. .
EUROPEAN JOURNAL OF CANCER, 2010, 46 (03) :642-649
[2]
Glioma stem cells promote radioresistance by preferential activation of the DNA damage response [J].
Bao, Shideng ;
Wu, Qiulian ;
McLendon, Roger E. ;
Hao, Yueling ;
Shi, Qing ;
Hjelmeland, Anita B. ;
Dewhirst, Mark W. ;
Bigner, Darell D. ;
Rich, Jeremy N. .
NATURE, 2006, 444 (7120) :756-760
[3]
Callaway T R, 2003, Curr Issues Intest Microbiol, V4, P43
[4]
The human AC133 hematopoietic stem cell antigen is also expressed in epithelial cells and targeted to plasma membrane protrusions [J].
Corbeil, D ;
Röper, K ;
Hellwig, A ;
Tavian, M ;
Miraglia, S ;
Watt, SM ;
Simmons, PJ ;
Peault, B ;
Buck, DW ;
Huttner, WB .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (08) :5512-5520
[5]
Phenotypic characterization of human colorectal cancer stem cells [J].
Dalerba, Piero ;
Dylla, Scott J. ;
Park, In-Kyung ;
Liu, Rui ;
Wang, Xinhao ;
Cho, Robert W. ;
Hoey, Timothy ;
Gurney, Austin ;
Huang, Emina H. ;
Simeone, Diane M. ;
Shelton, Andrew A. ;
Parmiani, Giorgio ;
Castelli, Chiara ;
Clarke, Michael F. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (24) :10158-10163
[6]
Tumour stem cells and drug resistance [J].
Dean, M ;
Fojo, T ;
Bates, S .
NATURE REVIEWS CANCER, 2005, 5 (04) :275-284
[7]
Cancer stem cells and radiotherapy: New insights into tumor radioresistance [J].
Diehn, Maximilian ;
Clarke, Michael F. .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2006, 98 (24) :1755-1757
[8]
Association of reactive oxygen species levels and radioresistance in cancer stem cells [J].
Diehn, Maximilian ;
Cho, Robert W. ;
Lobo, Neethan A. ;
Kalisky, Tomer ;
Dorie, Mary Jo ;
Kulp, Angela N. ;
Qian, Dalong ;
Lam, Jessica S. ;
Ailles, Laurie E. ;
Wong, Manzhi ;
Joshua, Benzion ;
Kaplan, Michael J. ;
Wapnir, Irene ;
Dirbas, Frederick M. ;
Somlo, George ;
Garberoglio, Carlos ;
Paz, Benjamin ;
Shen, Jeannie ;
Lau, Sean K. ;
Quake, Stephen R. ;
Brown, J. Martin ;
Weissman, Irving L. ;
Clarke, Michael F. .
NATURE, 2009, 458 (7239) :780-U123
[9]
The Stem Cell Marker CD133 Associates with Enhanced Colony Formation and Cell Motility in Colorectal Cancer [J].
Elsaba, Tarek M. A. ;
Martinez-Pomares, Luisa ;
Robins, Adrian R. ;
Crook, Simon ;
Seth, Rashmi ;
Jackson, Darryl ;
McCart, Amy ;
Silver, Andrew R. ;
Tomlinson, Ian P. M. ;
Ilyas, Mohammad .
PLOS ONE, 2010, 5 (05)
[10]
Survival of the fittest: Cancer stem cells in therapeutic resistance and angiogenesis [J].
Eyler, Christine E. ;
Rich, Jeremy N. .
JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (17) :2839-2845