Melatonin inhibits cell proliferation in a rat model of breast hyperplasia by mediating the PTEN/AKT pathway.

In the present study, a rat model of breast hyperplasia was established via the administration of estradiol benzoate and progesterone. Subsequent changes associated with breast hyperplasia were then investigated by measuring the diameter and height of the nipples and by staining breast tissue with hematoxylin and eosin. The proliferation and apoptosis of hyperplastic cells in the breast tissue were then determined by analyzing the expression of proliferating cell nuclear antigen (PCNA) and cleaved‑caspase‑3 by immunohistochemistry and TUNEL staining. We also determined the expression of proteins associated with the phosphatase and tensin homolog (PTEN)/protein kinase B (AKT) signaling pathway by western blotting. Melatonin treatment led to a significant reduction in the degree of breast hyperplasia (P<0.05), a significant reduction in PCNA, a significant increase in the level of apoptosis (P<0.05), a significant increase in PTEN (P<0.05), and a significant reduction in AKT/p‑AKT (P<0.05). Furthermore, melatonin significantly decreased the aggravation of breast hyperplasia induced by application of a PTEN inhibitor. Melatonin reduced the degree of breast hyperplasia, reduced the proliferation of hyperplastic breast tissue cells, and promoted cell apoptosis in hyperplastic tissue. These effects were achieved by the specific regulation of proteins in the PTEN/PI3K/AKT axis.