Metformin and Dapagliflozin Halt Breast Cancer Progression in Rats by Targeting microRNA-34a | ||||
| Bulletin of Egyptian Society for Physiological Sciences | ||||
| Volume 45, Issue 3, July 2025, Page 390-408 PDF (915.52 K) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/besps.2025.362566.1203 | ||||
 View on SCiNiTO | ||||
| Authors | ||||
Esraa S. Habiba   1; Mona Hassan Fathelbab 2; Marwa M. AbdElaziz 3; Eman A. Allam 4; Marwa Mahmoud Mady 5; Soha Elatrebi 1
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| 1Clinical pharmacology department, Faculty of Medicine, Alexandria University, Alexandria, Egypt. | ||||
| 2Medical Biochemistry Department. Faculty of Medicine, Alexandria University, Alexandria, Egypt. | ||||
| 3Pathology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt. | ||||
| 4Medical physiology department, faculty of medicine, Alexandria university | ||||
| 5Human Anatomy and Embryology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt Biomedical Science Department, Gulf Medical University | ||||
| Abstract | ||||
| Background: High glucose levels in breast cancer (BC) cells boost their spread and resistance to treatment by converting them into cancer stem cells. This study investigated the effects of anti-diabetic drugs metformin and dapagliflozin on tumor glucose and the role of miRNA-34a in DMBA-induced breast cancer in rats. Methods: Breast cancer was induced in 24 female Wistar rats using a single oral dose of DMBA. After a breast mass of 0.5 cm³ developed, the rats were divided into four groups: 8 received Metformin, 8 received Dapagliflozin, 8 remained untreated, and 8 were normal controls. Over five weeks, body weight and tumor size were monitored. At the end of the treatment, rats were euthanized, and blood and breast masses were collected to assess glucose, oxidative stress, ALDH-1, caspase 3, AMPK, and miRNA34a, breast tissue was also evaluated histopathologically. Results: Metformin and dapagliflozin reduced tumor volume and weight loss. While metformin-treated rats showed a partial pathological response, dapagliflozin-treated rats exhibited nearly normal breast tissue. Dapagliflozin significantly lowered glucose levels, oxidative stress indicators, and ALDH-1 compared to metformin, and enhanced caspase 3, AMPK, and miRNA-34a expression. Conclusion: Dapagliflozin and metformin combat DMBA-induced breast cancer by regulating glucose metabolism through the AMPK/miRNA 34a pathway. | ||||
| Keywords | ||||
| Breast Cancer; AMPK; miRNA 34a; Metformin; Dapagliflozin | ||||
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