Positive correlation of Oct4 and ABCG2 to chemotherapeutic resistance in CD90(+)CD133(+) liver cancer stem cells

Cell Reprogram. 2013 Apr;15(2):143-50. doi: 10.1089/cell.2012.0048. Epub 2013 Feb 25.

Abstract

Liver cancer is one of the most common tumors worldwide and drug resistance is a major obstacle to successful therapy. The growing data show that cancer stem cells (CSCs), a rare subpopulation of cancer cells, might be an important mechanism of drug resistance. To explore the self-renewal ability and chemotherapy resistance in liver CSCs, we enriched CD90(+)CD133(+) hepatocellular carcinoma (HCC) CSCs using sphere formation, which was accomplished by cultivating HCC CSCs from established HCC cell lines (HepG2 line and Hep3B line). Cell proliferation capacity was detected using colony formation assays, and cell activity was detected using methyl thiazolyl tetrazolium (MTT) assays after doxorubicin treatment. Expression of CD90, CD133, Oct4, and ABCG2 mRNA and protein levels was detected by PCR and western blot, respectively, which showed that these genes were significantly overexpressed in liver CSCs compared to parental cells (p<0.05). Oct4 and ABCG2 are highly expressed in enriched CD90(+)CD133(+) liver CSCs and are closely associated with chemotherapy drug resistance. We postulated that liver CSCs maybe the cause of high recurrence in liver cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / biosynthesis*
  • ATP-Binding Cassette Transporters / genetics
  • Antibiotics, Antineoplastic / pharmacology
  • Antigens, CD / biosynthesis*
  • Antigens, CD / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Doxorubicin / pharmacology
  • Drug Resistance, Neoplasm*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glycoproteins / biosynthesis*
  • Glycoproteins / genetics
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Octamer Transcription Factor-3 / biosynthesis*
  • Octamer Transcription Factor-3 / genetics
  • Peptides / genetics
  • Thy-1 Antigens / biosynthesis*
  • Thy-1 Antigens / genetics

Substances

  • ABCG2 protein, human
  • AC133 Antigen
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Antibiotics, Antineoplastic
  • Antigens, CD
  • Glycoproteins
  • Neoplasm Proteins
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • PROM1 protein, human
  • Peptides
  • Thy-1 Antigens
  • Doxorubicin