Further characterization of cyclophosphamide resistance: expression of CD95 and of bcl-2 in a CML cell line

Leuk Res. 1998 Nov;22(11):1073-7. doi: 10.1016/s0145-2126(98)00093-9.

Abstract

Drug resistance is a common cause of treatment failure in oncology. In addition to the resistance caused by over-expression of p-glycoprotein and similar molecules other mechanisms are involved in the selection or induction of drug resistant tumor cells. In this study, we characterized a CML cell line made resistant to cyclophosphamide (KBM7-B5-1803) further for the expression of apoptosis promoting and inhibiting molecules. We found that KBM7-B5-1803 has a 3 4-fold over-expression of the receptor CD95 (Fas/Apo-1) compared with the parent line. The regulation of CD95 by cytokines was comparable to other types of cells. Despite the inducibility and over-expression of CD95, CD95 failed to trigger apoptosis in both the parent and the drug resistant line. The drug resistant line has a particular pattern of the expression of bcl-2 family members: bcl-2 protein and message were expressed to a similar extent, however, compared with the parent line, the message for bclx short was decreased. P-glycoprotein was not expressed in either cell line. Taken together we show here in a leukemia cell line that the phenotype of cyclophosphamide resistance is associated with a particular pattern of apoptosis-related molecules.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis / drug effects
  • Cyclophosphamide / pharmacology*
  • Drug Resistance, Neoplasm
  • Humans
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured
  • fas Receptor / metabolism*

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • fas Receptor
  • Cyclophosphamide