Simulation model of doxorubicin activity in islets of human breast cancer cells

Jan Lankelma, Rafael Fernández Luque, Henk Dekker, Herbert M. Pinedo

Research output: Contribution to journalArticle

Abstract

During cytotoxic chemotherapy, cancer cells are exposed to a dynamic concentration-versus-time curve. Besides the area under this curve, the shape of this curve may determine the cytotoxic effect. This report describes the concept that cell damage is determined by the molar drug accumulation history inside the tumor cells. Cell numbers of large populations of human MCF-7 cells exposed to three different doxorubicin concentration-versus-time profiles were recorded for 31 days. The drug accumulation history in the cells was calculated using cellular drug transport parameters derived from doxorubicin uptake and efflux measurements on MCF-7 cells attached to culture dishes. Recovery of the proliferation rate of a cell population after drug exposure was described using a mathematical model of cell damage. The model fitted well to the proliferation assays. It allowed for comparison of the effects of changes in doxorubicin concentration-versus-time profiles in vitro. The model was then used to predict the effect of the changes in the doxorubicin concentration profile in vivo, in tumor islets, after a bolus injection of doxorubicin. In the model doxorubicin exposure resulted in less cell damage inside the tumor islets than at the rim.

Original languageEnglish (US)
Pages (from-to)169-178
Number of pages10
JournalBiochimica et Biophysica Acta - General Subjects
Volume1622
Issue number3
DOIs
StatePublished - Aug 22 2003
Externally publishedYes

Fingerprint

Doxorubicin
Cells
Breast Neoplasms
Tumors
Pharmaceutical Preparations
MCF-7 Cells
Neoplasms
History
Chemotherapy
Assays
Population
Area Under Curve
Mathematical models
Theoretical Models
Cell Count
Recovery
Drug Therapy
Injections

Keywords

  • Breast cancer
  • Drug transport
  • Mathematical model
  • Pharmacodynamic
  • Target concentration

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Simulation model of doxorubicin activity in islets of human breast cancer cells. / Lankelma, Jan; Fernández Luque, Rafael; Dekker, Henk; Pinedo, Herbert M.

In: Biochimica et Biophysica Acta - General Subjects, Vol. 1622, No. 3, 22.08.2003, p. 169-178.

Research output: Contribution to journalArticle

Lankelma, Jan ; Fernández Luque, Rafael ; Dekker, Henk ; Pinedo, Herbert M. / Simulation model of doxorubicin activity in islets of human breast cancer cells. In: Biochimica et Biophysica Acta - General Subjects. 2003 ; Vol. 1622, No. 3. pp. 169-178.
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