Department of Outpatient, Chengdu Aurora Huan Hua Xiang, Chengdu, Sichuan, 610072, China.
Department of Gynecology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, China.
J Environ Pathol Toxicol Oncol. 2021;40(3):51-61. doi: 10.1615/JEnvironPatholToxicolOncol.2021038118.
To investigate the anticancer mechanism of neferine on DMBA-prompted mammary tumorigenesis in animals.
Mammary cancer was prompted by the subcutaneous injection of 25 mg DMBA mixed in 1 ml of the vehicle (sunflower oil [0.5 ml] and saline [0.5 ml]). We analyzed the biochemical and molecular expression of cell-proliferation and apoptotic markers in normal and DMBA-induced rats.
We detected low body weight, elevated quantities of lipid peroxidation, and low antioxidant enzyme activities in mammary tissues of DMBA-induced animals. We also found an invasive ductal carcinoma in DMBA-induced animals by histopathological assessment. Furthermore, western blotting findings displayed an augmented expression of PI3K, AKT, NF-κB, PCNA, cyclin D1, Ki-67, and Bcl-2, while reducing expression of p53, Bax, caspase-3, and caspase-9 in DMBA-induced cancer-bearing animals. RT-PCR results found upregulation of cyclin D1, PCNA, and Ki-67, and reduced expression of p53 in DMBA-prompted animals. The oral administration of neferine effectually inhibited mammary tumors via improved antioxidants and prevented lipid peroxidation activities when compared with tumor-bearing rats. Furthermore, neferine also modulated PI3K/AKT/NF-κB signaling through inhibiting cell proliferation and induced apoptosis in tumor-bearing rats.
In our findings, we concluded that neferine has an anti-proliferative and enhancing apoptotic property against DMBA-induced mammary cancer.
研究小檗碱对 DMBA 诱发动物乳腺肿瘤发生的抗癌机制。
通过皮下注射 25mg 溶于 1ml 载体（葵花籽油[0.5ml]和生理盐水[0.5ml]）的 DMBA 来诱发乳腺癌。我们分析了正常和 DMBA 诱导大鼠中细胞增殖和凋亡标志物的生化和分子表达。
我们在 DMBA 诱导动物的乳腺组织中检测到低体重、脂质过氧化产物增加和抗氧化酶活性降低。通过组织病理学评估，我们还发现 DMBA 诱导动物存在浸润性导管癌。此外，Western blot 结果显示，PI3K、AKT、NF-κB、PCNA、cyclin D1、Ki-67 和 Bcl-2 的表达增加，而 p53、Bax、caspase-3 和 caspase-9 的表达减少。RT-PCR 结果发现，DMBA 诱导动物的 cyclin D1、PCNA 和 Ki-67 上调，p53 下调。与荷瘤大鼠相比，小檗碱的口服给药通过改善抗氧化剂和防止脂质过氧化活性有效地抑制了乳腺肿瘤。此外，小檗碱还通过抑制细胞增殖和诱导荷瘤大鼠凋亡来调节 PI3K/AKT/NF-κB 信号通路。
在我们的研究结果中，我们得出结论，小檗碱对 DMBA 诱导的乳腺肿瘤具有抗增殖和增强凋亡的作用。
