P-glycoprotein is not involved in pathway of anti-Fas/Fas-induced apoptosis in KBv200 cells

World J Gastroenterol. 2005 Jun 21;11(23):3544-8. doi: 10.3748/wjg.v11.i23.3544.


Aim: To verify whether P-glycoprotein (P-gp) could induce cell resistance to apoptosis by inhibiting caspase-8 and caspase-3.

Methods: Human KB cells, either drug-sensitive or with multidrug resistance (MDR) phenotype caused by overexpression of P-gp (KBv200 cells), were treated with anti-Fas (CH-11 monoclonal antibody) to induce apoptosis. Cytotoxicity was detected by MTT assay. Symptoms of cell death were assessed by morphological observation after Hoechst33258 staining, activation of caspase-8 and caspase-3 was measured by Western blotting.

Results: Compared with KB cells, the resistance of KBv200 cells to VCR (vincristine) was about 51-fold higher. Anti-Fas (CH-11) induced cytotoxicity and apoptosis in both sensitive KB cells and MDR phenotype KBv200 cells. The IC50 of CH-11 in KB cells was similar to that in KBv200 cells. CH-11 induced similar apoptotic rates in both KB cells and KBv200 cells, which could be classified as caspase-dependent apoptotic pathway. Verapamil (VRP) did not affect CH-11-mediated apoptosis in KBv200 cells.

Conclusion: Expression of P-glycoprotein does not induce resistance to caspase-8 and -3 activation or anti-Fas-induced cell apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Antibodies, Monoclonal / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Caspase 3
  • Caspase 8
  • Caspases / metabolism
  • Drug Resistance, Multiple
  • Humans
  • KB Cells
  • Vincristine / toxicity
  • fas Receptor / immunology
  • fas Receptor / physiology*


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antibodies, Monoclonal
  • fas Receptor
  • Vincristine
  • CASP3 protein, human
  • CASP8 protein, human
  • Caspase 3
  • Caspase 8
  • Caspases