Persistence of side population cells with high drug efflux capacity in pancreatic cancer

World J Gastroenterol. 2008 Feb 14;14(6):925-30. doi: 10.3748/wjg.14.925.

Abstract

Aim: To investigate the persistence of side population (SP) cells in pancreatic cancer and their role and mechanism in the drug resistance.

Methods: The presentation of side population cells in pancreatic cancer cell line PANC-1 and its proportion change when cultured with Gemcitabine, was detected by Hoechst 33342 staining and FACS analysis. The expression of ABCB1 and ABCG2 was detected by real-time PCR in either SP cells or non-SP cells.

Results: SP cells do exist in PANC-1, with a median of 3.3% and a range of 2.1-8.7%. After cultured with Gemcitabine for 3 d, the proportion of SP cells increased significantly (3.8% +/- 1.9%, 10.7% +/- 3.7%, t = 4.616, P = 0.001 < 0.05). ABCB1 and ABCG2 expressed at higher concentrations in SP as compared with non-SP cells (ABCB1: 1.15 +/- 0.72, 5.82 +/- 1.16, t = 10.839, P = 0.000 < 0.05; ABCG2: 1.16 +/- 0.75, 5.48 +/- 0.94, t = 11.305, P = 0.000 < 0.05), which may contribute to the efflux of fluorescent staining and drug resistance.

Conclusion: SP cells with inherently high resistance to chemotherapeutic agents do exist in pancreatic cancers, which may be candidate cancer stem cells contributing to the relapse of the tumor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Antimetabolites, Antineoplastic / metabolism
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Cell Shape
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / metabolism
  • Drug Resistance, Neoplasm*
  • Gemcitabine
  • Humans
  • Neoplastic Stem Cells / cytology
  • Neoplastic Stem Cells / physiology*
  • Pancreatic Neoplasms* / metabolism
  • Pancreatic Neoplasms* / pathology

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP-Binding Cassette Transporters
  • Antimetabolites, Antineoplastic
  • Biomarkers, Tumor
  • TAP1 protein, human
  • Deoxycytidine
  • Gemcitabine