Department of Surgical Oncology, Wenzhou Central Hospital, Wenzhou, Zhejiang 325000, P.R. China.
Department of Surgical Oncology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310005, P.R. China.
Oncol Rep. 2021 May;45(5). doi: 10.3892/or.2021.8017. Epub 2021 Jun 29.
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.
在本研究中，通过给予苯甲酸雌二醇和孕酮建立了大鼠乳腺增生模型。然后通过测量乳头的直径和高度以及用苏木精和伊红对乳腺组织进行染色来研究与乳腺增生相关的变化。通过免疫组织化学和 TUNEL 染色分析增殖细胞核抗原（PCNA）和裂解的胱天蛋白酶-3的表达，来确定乳腺组织中增生细胞的增殖和凋亡。我们还通过 Western blot 确定了与磷酸酶和张力蛋白同源物（PTEN）/蛋白激酶 B（AKT）信号通路相关的蛋白的表达。褪黑素治疗导致乳腺增生程度显著降低（P<0.05），PCNA 显著降低，凋亡水平显著升高（P<0.05），PTEN 显著升高（P<0.05），AKT/p-AKT 显著降低（P<0.05）。此外，褪黑素显著降低了 PTEN 抑制剂应用引起的乳腺增生的加重。褪黑素降低了乳腺增生的程度，降低了增生性乳腺组织细胞的增殖，并促进了增生组织中的细胞凋亡。这些作用是通过对 PTEN/PI3K/AKT 轴中的蛋白质进行特异性调节来实现的。
