Document Type : Original Article
Authors
1
Clinical pharmacology department, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
2
Medical Biochemistry Department. Faculty of Medicine, Alexandria University, Alexandria, Egypt.
3
Pathology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
4
Medical physiology department, faculty of medicine, Alexandria university
5
Human 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.
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