Targeting BCRP/ABCG2 by RNA interference enhances the chemotherapy sensitivity of human colon cancer side population cells

J Huazhong Univ Sci Technolog Med Sci. 2017 Apr;37(2):231-236. doi: 10.1007/s11596-017-1720-1. Epub 2017 Apr 11.

Abstract

Relapse and metastasis are frequent in colon cancer and may be linked to stem cell characteristics. This study isolated side population (SP) cells from a colon cancer cell line (Colo-320) and examined their self-renewal and differentiation abilities. Compared to non-SP (NSP) cells, SP colon cancer cells were more tumorigenic in vivo and exhibited more invasive characteristics and a greater ability to form colonies. Additionally, more cells were in G0/G1 phase and more highly expressed the multidrug resistance protein BCRP/ABCG2. We achieved enhanced chemotherapy sensitivity by transfecting SP cells with a hairpin-like, small interfering RNA (siRNA) eukaryotic expression plasmid targeting BCRP/ABCG2.

Keywords: RNAi; bcrp/abcg2; chemotherapy sensitivity; colon cancer; side population cells.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / antagonists & inhibitors*
  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / genetics
  • Animals
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / therapy*
  • Drug Synergism
  • Drug Therapy
  • Fluorouracil / administration & dosage*
  • Fluorouracil / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Mice
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / genetics
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / pathology
  • RNA, Small Interfering / pharmacology*
  • Side-Population Cells / drug effects*
  • Side-Population Cells / pathology
  • Xenograft Model Antitumor Assays

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • Neoplasm Proteins
  • RNA, Small Interfering
  • Fluorouracil