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Diane-35 and Metformin Induce Autophagy and Apoptosis in Polycystic Ovary Syndrome Women with Early-Stage Endometrial Carcinoma.
- Source :
-
Genes [Genes (Basel)] 2022 Jan 12; Vol. 13 (1). Date of Electronic Publication: 2022 Jan 12. - Publication Year :
- 2022
-
Abstract
- Objective: Women with polycystic ovary syndrome (PCOS) are at increased risk ofendometrial carcinoma (EC). Previous studies indicated that the combined therapy of Diane-35 and metformin significantly suppresses disease progression in PCOS patients with early EC; however, the mechanisms remain unclear.<br />Methods: An established murine model of PCOS with early EC, clinical specimens, and human EC cells was used in this study. The levels of protein and mRNA were measured with Western blotting and RT-PCR, respectively. Cell proliferation was determined with MTT, colony formation, and flow cytometry. Proteins were analyzed with immunofluorescence and immunohistochemistry.<br />Results: Diane-35 and metformin significantly inhibited proliferative activity and promoted apoptosis in EC cells. Additionally, cell autophagy was induced by the combined therapy. Quantitive PCR revealed that Diane-35 and metformin decreased androgen receptor (AR) expression but elevated GLUT4 expression. AR was found to repress GLUT4 expression by binding to the promoter of GLUT4. Moreover, the combined treatment mediated the onset of cellular autophagy by regulating the mTORC pathway via the suppression of IGF-1 and inhibited the development of EC by the activation of the PI3K/mTORC pathway.<br />Conclusion: The results and previous clinical evidence support the use of Diane-35 and metformin combination therapy for patients with PCOS and early EC.
- Subjects :
- Androgen Antagonists pharmacology
Animals
Drug Combinations
Drug Therapy, Combination
Endometrial Neoplasms etiology
Endometrial Neoplasms metabolism
Endometrial Neoplasms pathology
Female
Glucose Transporter Type 4 genetics
Glucose Transporter Type 4 metabolism
Hypoglycemic Agents pharmacology
Insulin-Like Growth Factor I antagonists & inhibitors
Mice
Receptors, Androgen chemistry
Apoptosis
Autophagy
Cyproterone Acetate pharmacology
Endometrial Neoplasms drug therapy
Ethinyl Estradiol pharmacology
Metformin pharmacology
Polycystic Ovary Syndrome complications
Subjects
Details
- Language :
- English
- ISSN :
- 2073-4425
- Volume :
- 13
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Genes
- Publication Type :
- Academic Journal
- Accession number :
- 35052471
- Full Text :
- https://doi.org/10.3390/genes13010131