Flow cytometric analysis of P-glycoprotein expression and drug efflux in human soft tissue and bone sarcomas

Hiroshi Kunikane, Mark M. Zalupski, Cheppail Ramachandran, Mark A. Kukuruga, David Lucas, James R. Ryan, Awtar Krishan

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Twenty-two fresh surgical specimens of human sarcomas (soft tissue and bone) from 20 patients were analyzed by flow cytometry for the expression of drug resistance-related P-glycoprotein (P-gp) and cellular daunorubicin (DNR) accumulation with or without the presence of DNR efflux blockers. Single-cell suspensions prepared from the tumor specimens were analyzed by dual-color flow cytometry after reaction with MRK-16 (anti-P-gp) and anti- CD45 (pan-leukocyte) antibodies. MRK-16 reactivity of tumor cells was evaluated after exclusion of CD45-positive cells by electronic gates. Parallel samples were incubated with DNR alone or in combination with DNR efflux blockers, verapamil (VPL), or dipyridamole (DPD) for determination of cellular DNR accumulation and the effect of the efflux blockers. Extensive heterogeneity was observed in both P-gp expression and DNR accumulation of the tumor specimens examined. Eight of the 22 tumor specimens had significant numbers of P-gp-positive cells. In three of the eight P-gp- positive tumors, cellular DNR accumulation was significantly increased by co-incubation with the efflux blockers VPL or DPD. These results indicate that both quantitative and functional analysis of P-gp expression may he essential in determining the cellular drug resistance phenotype of tumor cells and its correlation with therapeutic outcome.

Original languageEnglish (US)
Pages (from-to)197-203
Number of pages7
JournalCommunications in Clinical Cytometry
Volume30
Issue number4
DOIs
StatePublished - Aug 15 1997

Keywords

  • Bone sarcoma
  • Daunorubicin
  • Drug efflux
  • Flow cytometry
  • Multidrug resistance
  • P- glycoprotein
  • Soft tissue sarcoma

ASJC Scopus subject areas

  • Hematology
  • Cell Biology
  • Pathology and Forensic Medicine
  • Biophysics
  • Endocrinology

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