In vitro effects of imatinib mesylate on radiosensitivity and chemosensitivity of breast cancer cells.
BACKGROUND
Breast cancer treatment is based on a combination of adjuvant chemotherapy followed by radiotherapy effecting intracellular signal transduction. With the tyrosine kinase inhibitors new targeted drugs are available. Imatinib mesylate is a selective inhibitor of bcr-abl, PRGFR alpha, beta and c-kit. The purpose of this study was to determine whether Imatinib has an influence on the effectiveness of radiotherapy in breast cancer cell lines and if a combination of imatinib with standard chemotherapy could lead to increased cytoreduction.


METHODS
Colony-forming tests of MCF 7 and MDA MB 231 were used to study differences in cell proliferation under incubation with imatinib and radiation. Changes in expression and phosphorylation of target receptors were detected using western blot. Cell proliferation, migration and apoptosis assays were performed combining imatinib with doxorubicin.


RESULTS
The combination of imatinib and radiotherapy showed a significantly stronger inhibition of cell proliferation compared to single radiotherapy. Differences in PDGFR expression could not be detected, but receptor phosphorylation was significantly inhibited when treated with imatinib. Combination of imatinib with standard chemotherapy lead to an additive effect on cell growth inhibition compared to single treatment.


CONCLUSIONS
Imatinib treatment combined with radiotherapy leads in breast cancer cell lines to a significant benefit which might be influenced through inhibition of PDGFR phosphorylation. Combining imatinib with chemotherapy enhances cytoreductive effects. Further in vivo studies are needed to evaluate the benefit of Imatinib in combination with radiotherapy and chemotherapy on the treatment of breast cancer.
Weigel
Marion T
MT
Department of Obstetrics and Gynecology, Breast Center, University of Kiel, Arnold-Heller Strasse 3, 24105 Kiel, Germany.
Dahmke
Linda
L
Schem
Christian
C
Bauerschlag
Dirk O
DO
Weber
Katrin
K
Niehoff
Peter
P
Bauer
Maret
M
Strauss
Alexander
A
Jonat
Walter
W
Maass
Nicolai
N
Mundhenke
Christoph
C
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001549:Benzamides; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D002448:Cell Adhesion / Q000187:drug effects / Q000528:radiation effects; D002465:Cell Movement / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D003037:Cobalt Radioisotopes; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000528:radiation effects*; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D007496:Iridium Radioisotopes; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D010879:Piperazines / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage; D011836:Radiation Tolerance / Q000187:drug effects* / Q000528:radiation effects; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D001549:Benzamides; D003037:Cobalt Radioisotopes; D007496:Iridium Radioisotopes; D010879:Piperazines; D011743:Pyrimidines; D004317:Doxorubicin; D000068877:Imatinib Mesylate; D020797:Receptor, Platelet-Derived Growth Factor beta