In vitro downregulation of growth factors by insulin-like growth factor binding protein-3 in cervical cancer.
Gynecol Oncol
; 91(2): 410-5, 2003 Nov.
Article
en En
| MEDLINE
| ID: mdl-14599874
ABSTRACT
OBJECTIVES:
Our hypothesis is that insulin-like growth factor binding protein 3 (IGF-BP3) would downregulate epidermal growth factor receptor (EGF-R) levels in cervical cancer cell lines, thereby reducing cellular IGF-II and angiogenesis-related vascular endothelial cell growth factor (VEGF). As folate deficiency is a risk factor in cervical cancer, we sought to determine if folic acid treatment might increase IGF-BP3 production, thereby inhibiting malignant cell proliferation.METHODS:
We determined the cellular levels of EGF-R, IGF-II, and VEGF in the cervical cancer cell lines HeLa, ME-180 (both positive for human papilloma virus; HPV), and HT-3 (HPV-negative), following their treatment with IGF-BP3. Levels of IGF-BP3 in these cells before and after treatment with folic acid and VEGF were also enumerated, using a computerized semiquantitative immunofluorescent antibody assay.RESULTS:
Treatment with IGF-BP3 significantly reduced the levels (mean intensity per pixel) of EGF-R, IGF-II, and VEGF in all three cell lines and IGF-I receptor (IGF-IR) in representative ME-180 cell line. Treatment with antiproliferative folic acid increased IGF-BP3 levels while the proliferative VEGF depleted cellular IGF-BP3 in all the cell lines.CONCLUSIONS:
Levels of EGF-R, IGF-II, IGF-IR, and VEGF are significantly reduced following treatment with IGF-BP3 in cervical cancer. We observed increased levels of IGF-BP3 by folic acid, and decreased IGF-BP3 levels by VEGF. Downregulation of EGF-R by IGF-BP3 suggests an IGF-independent action. Folate deficiency is a risk factor in cervical cancer. Our results suggest that folic acid supplementation can lead to inhibition of cervical cancer cell growth by promoting increased IGF-BP3 levels.
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Bases de datos:
MEDLINE
Asunto principal:
Factor II del Crecimiento Similar a la Insulina
/
Neoplasias del Cuello Uterino
/
Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina
/
Factor A de Crecimiento Endotelial Vascular
/
Receptores ErbB
Tipo de estudio:
Risk_factors_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
Gynecol Oncol
Año:
2003
Tipo del documento:
Article
País de afiliación:
Estados Unidos