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Published on: February 9, 2024
In vitro downregulation of growth factors by insulin-like growth factor binding protein-3 in cervical cancer
Rajesh S Mathur1, Subbi P Mathur
1Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC 29425, USA. mathurs@musc.edu
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.
Insights
Insulin-like growth factor binding protein 3 (IGF-BP3) reduces cervical cancer cell growth by downregulating epidermal growth factor receptor (EGF-R). Folic acid increases IGF-BP3, inhibiting cancer proliferation.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Cervical cancer is linked to folate deficiency.
- Epidermal growth factor receptor (EGF-R) and insulin-like growth factors (IGFs) play roles in cancer progression.
- Insulin-like growth factor binding protein 3 (IGF-BP3) is a potential tumor suppressor.
Purpose of the Study:
- To investigate the effect of IGF-BP3 on EGF-R, IGF-II, and vascular endothelial cell growth factor (VEGF) in cervical cancer cell lines.
- To determine if folic acid supplementation can increase IGF-BP3 production and inhibit cervical cancer cell proliferation.
Main Methods:
- Cervical cancer cell lines (HeLa, ME-180, HT-3) were treated with IGF-BP3.
- Cellular levels of EGF-R, IGF-II, VEGF, and IGF-BP3 were measured using immunofluorescence assays.
- The impact of folic acid and VEGF on IGF-BP3 levels was assessed.
Main Results:
- IGF-BP3 treatment significantly reduced EGF-R, IGF-II, and VEGF levels in all tested cell lines.
- Folic acid treatment increased cellular IGF-BP3 levels.
- Vascular endothelial cell growth factor (VEGF) depleted cellular IGF-BP3.
Conclusions:
- IGF-BP3 effectively downregulates key growth factors (EGF-R, IGF-II, VEGF) in cervical cancer cells.
- Folic acid supplementation enhances IGF-BP3 production, suggesting a mechanism for inhibiting cervical cancer cell growth.
- These findings highlight a potential therapeutic role for folic acid in managing cervical cancer.
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