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Metformin Promotes Anti-tumor Biomarkers in Human Endometrial Cancer Cells
John Mark P Pabona1, Alexander F Burnett2,3, Dustin M Brown1
1Department of Physiology & Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Reproductive Sciences (Thousand Oaks, Calif.)
|February 13, 2020
Summary
Metformin (MET) may help prevent endometrial cancer (EC) in non-diabetic women. MET altered key protein expressions in tumors, suggesting a direct effect on cancer cells and signaling pathways.
Area of Science:
- Oncology
- Endocrinology
- Pharmacology
Background:
- Metformin (MET) is linked to reduced cancer incidence in diabetic patients.
- Its role in non-diabetic women with endometrial cancer (EC) is unknown.
Purpose of the Study:
- To investigate MET's effects on EC in obese, non-diabetic women.
- To analyze molecular changes in tumors after MET treatment.
Main Methods:
- Pilot study with randomized assignment to MET or control (CON) group.
- Analysis of tumor tissue for proliferation (Ki67), apoptosis (TUNEL), and protein expression (ERα, PGR, PTEN, KLF9).
- In vitro study using Ishikawa endometrial cancer cells treated with MET.
Main Results:
- MET increased PGR and KLF9 in glandular epithelial cells and PTEN in stromal cells, while decreasing ERα in glandular epithelial cells.
- No significant differences in proliferation (Ki67) or apoptosis (TUNEL) between groups.
- MET altered mRNA levels of key biomarkers in vitro and modulated PGR and KLF4 expression when KLF9 was reduced.
Conclusions:
- Metformin directly impacts endometrial cancer cells, modifying steroid receptor expression and signaling.
- MET may offer a preventative strategy for high-risk, non-diabetic women against endometrial cancer.
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