Liver cancer stem cells are selectively enriched by low-dose cisplatin.
Accumulating evidence has indicated the importance of cancer stem cells in carcinogenesis. The goal of the present study was to determine the effect of low-dose cisplatin on enriched liver cancer stem cells (LCSCs). Human hepatoblastoma HepG2 cells were treated with concentrations of cisplatin ranging from 1 to 5 μg/mL. Cell survival and proliferation were evaluated using a tetrazolium dye (MTT) assay. LCSCs were identified using specific markers, namely aldehyde dehydrogenase-1 (ALDH1) and CD133. The percentage of ALDH1+ or CD133+ cells was examined by flow cytometric analysis. The expression of ALDH1 and/or CD133 in HepG2 cells was determined by immunocytochemical analysis. Low-dose cisplatin treatment significantly decreased cell survival in HepG2 cells after 24 or 72 h. However, the percentage of LCSCs in the surviving cells was greatly increased. The percentage of ALDH1+ or CD133+ cells was increased in a time- and dose-dependent manner after treatment with 1-4 μg/mL cisplatin, whereas 5 μg/mL cisplatin exposure slightly reduced the number of positive cells. These findings indicate that low-dose cisplatin treatment may efficiently enrich the LCSC population in HepG2 cells.
Department of Internal Medicine, First Affiliated Hospital, Dalian Medical University, Dalian, China.
H
H
Zhang
Department of Internal Medicine, First Affiliated Hospital, Dalian Medical University, Dalian, China.
W J
WJ
Chang
Department of Internal Medicine, First Affiliated Hospital, Dalian Medical University, Dalian, China.
X Y
XY
Li
Department of Internal Medicine, First Affiliated Hospital, Dalian Medical University, Dalian, China.
N
N
Zhang
Department of Internal Medicine, First Affiliated Hospital, Dalian Medical University, Dalian, China.
J J
JJ
Kong
Department of Internal Medicine, First Affiliated Hospital, Dalian Medical University, Dalian, China.
Y F
YF
Wang
D000071916:AC133 Antigen; D000080924:Aldehyde Dehydrogenase 1 Family; D015703:Antigens, CD / Q000032:analysis; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000032:analysis; D063646:Carcinogenesis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage* / Q000627:therapeutic use; D005434:Flow Cytometry; D006023:Glycoproteins / Q000032:analysis; D056945:Hep G2 Cells; D018197:Hepatoblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000187:drug effects*; D010455:Peptides / Q000032:analysis; D050697:Retinal Dehydrogenase / Q000032:analysis; D013778:Tetrazolium Salts
D000071916:AC133 Antigen; D015703:Antigens, CD; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D006023:Glycoproteins; D007527:Isoenzymes; C000606023:PROM1 protein, human; D010455:Peptides; D013778:Tetrazolium Salts; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase; D002945:Cisplatin