Liver cancer stem cells are selectively enriched by low-dose cisplatin.

H Zhang,X.Y Li,N Zhang,J.J Kong,Y.F Wang,W.J Chang

doi:10.1590/1414-431x20143415

Abstract

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.

Highlights

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and the leading cause of cancer mortality [1]
These findings indicate that low-dose cisplatin treatment may efficiently enrich the liver cancer stem cells (LCSCs) population in HepG2 cells
Compared to 24 h, prolonged cisplatin exposure (72 h) significantly enhanced cell death (P,0.05). These data indicate that cisplatin treatment reduced survival of HepG2 cells

Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and the leading cause of cancer mortality [1]. Understanding of the molecular mechanisms involved in the initiation and progression of HCC has been increasing, data on the impact of cancer stem cells on hepatocarcinogenesis are inconsistent [2]. HCC is thought to be comprised of morphologically diverse cell types that express a variety of hepatic lineage markers. Chiba et al [4] reported that subpopulations of cancer stem cells exist in some HCC cell lines, including the human liver cancer cell lines, Huh and PLC/PRF/5. Cancer stem cells are closely associated with the recurrence and metastasis of tumors [5,6]. The identification and characterization of liver cancer stem cells (LCSCs) in HCC cells may help to develop effective and targeted therapies

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