Changes in vascular endothelial growth factor (VEGF) after chemoendocrine therapy in breast cancer.
OBJECTIVE
Angiogenesis has been proposed as a possible target for anticancer treatment, either by inhibition of the production of angiogenic factors or by inhibition of endothelial cell proliferation. The impact of preoperative chemoendocrine therapy is unknown in the regulation of angiogenic factors, but recent reports suggest that anticancer drugs have antiangiogenic activity.


METHODS
The expression of two angiogenic factors VEGF and Angiopoetin-1 were quantified at different concentrations of doxorubicin, docetaxel, tamoxifen, exemestane and letrozol on MCF-7 and T47D cells.


RESULTS
Low-drug concentrations led to increased VEGF-A gene transcription whereas high (10-fold increased) drug concentrations suppressed gene expression. A similar cell reaction was observed for VEGF protein with a smaller variety in the extent of modulation. Incubation of MCF-7 cells to different drugs showed a similar dose-dependent modulation of Angiopoietin-1 gene expression with enhancement at low-drug concentrations.


CONCLUSIONS
Treatment of breast cancer cells following a preoperative protocol showed a dose-dependent expression of VEGF and Angiopoetin-1. Only high-drug concentrations were followed by a decreased secretion of both factors whereas low concentrations induced up-regulation of VEGF and Angiopoietin 1.
Fersis
N
N
Breast Clinic, Department of Gynecology, University of Tübingen, Germany.
Smyczek-Gargya
B
B
Armeanu
S
S
Gagulic
E
E
Pantic
L
L
Relakis
K
K
Friedrich
M
M
Wallwiener
D
D
D000730:Androstadienes / Q000008:administration & dosage / Q000494:pharmacology; D042683:Angiopoietin-1 / Q000096:biosynthesis*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D017931:DNA Primers; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000077289:Letrozole; D009389:Neovascularization, Pathologic; D009570:Nitriles / Q000008:administration & dosage / Q000494:pharmacology; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013629:Tamoxifen / Q000008:administration & dosage / Q000494:pharmacology; D043823:Taxoids / Q000008:administration & dosage / Q000494:pharmacology; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000187:drug effects
D000730:Androstadienes; D042683:Angiopoietin-1; D000970:Antineoplastic Agents; D017931:DNA Primers; D009570:Nitriles; D012334:RNA, Neoplasm; D043823:Taxoids; D014230:Triazoles; D042461:Vascular Endothelial Growth Factor A; D013629:Tamoxifen; D000077143:Docetaxel; D000077289:Letrozole; D004317:Doxorubicin; C056516:exemestane