Yang Kehong, Xie Zhuzhu, Liu Shiao, Xu Ruilong, Mao Jie, Feng Wenjing, Zhao Xinya, Dai Yuqi, Zou Ying, Qian Rongkang, Qian Ronghua
Medical School, Hunan University of Chinese Medicine, Changsha, 410208, China.
Hunan Liwen Information Consulting Service Co., LTD., Changsha, 410005, China.
Med Oncol. 2025 Jul 21;42(8):358. doi: 10.1007/s12032-025-02917-9.
Breast cancer poses a significant threat to women's health globally, exhibiting the greatest incidence and fatality rates among female cancers. Chemotherapy is frequently employed in the clinical management of breast cancer. While the majority of patients require novel chemotherapeutic agents due to treatment resistance. We sought to examine the impact of ursolic acid (UA) on apoptosis and autophagy levels in breast cancer through Polo-like Kinase 1 (PLK1) via the AKT/mTOR signaling pathway. Tamoxifen (TAM) and adriamycin (ADM) served as positive control agents. In vitro experiments, the MTT assay was utilized to evaluate the viability of MCF-7/MDA-MB-231 cells, flow cytometry and JC-1 staining to analyze apoptosis, electron microscopy and MDC staining to scrutinize autophagy, and Western blot (WB) to measure the expression of pertinent proteins. In vivo research utilized the BALB/c mouse breast cancer model established with 4T1, comparing the volume and weight of transplanted tumors across several groups. Tumor necrosis was identified using HE staining, anti-apoptotic protein Bcl-2 expression was assessed via IHC labeling, and protein expression was evaluated using WB. UA suppressed tumor proliferation in BALB/c mice models of breast cancer. Tumor proliferation was markedly suppressed in the TAM and medium/high-dose UA cohorts. HE staining demonstrated significant necrosis, while IHC/WB analysis validated that UA or UA combined with Volasertib may reduce levels of Bcl-2, PLK1, p-AKT/AKT, and p-mTOR/mTOR, in conjunction with increased LC3 II/I. In conclusion, the study revealed that UA may affect the apoptosis and autophagy of breast cancer through PLK1 via AKT/mTOR signaling pathway.
乳腺癌对全球女性健康构成重大威胁，在女性癌症中发病率和死亡率最高。化疗常用于乳腺癌的临床治疗。然而，由于治疗耐药性，大多数患者需要新型化疗药物。我们试图通过Polo样激酶1（PLK1）经由AKT/mTOR信号通路研究熊果酸（UA）对乳腺癌细胞凋亡和自噬水平的影响。他莫昔芬（TAM）和阿霉素（ADM）作为阳性对照药物。在体外实验中，采用MTT法评估MCF-7/MDA-MB-231细胞的活力，流式细胞术和JC-1染色分析细胞凋亡，电子显微镜和MDC染色检查自噬，蛋白质免疫印迹法（WB）检测相关蛋白的表达。体内研究利用4T1建立的BALB/c小鼠乳腺癌模型，比较各组移植瘤的体积和重量。采用苏木精-伊红（HE）染色鉴定肿瘤坏死情况，免疫组化（IHC）标记评估抗凋亡蛋白Bcl-2的表达，WB评估蛋白表达。UA抑制BALB/c小鼠乳腺癌模型中的肿瘤增殖。TAM组和中/高剂量UA组的肿瘤增殖明显受到抑制。HE染色显示明显坏死，而IHC/WB分析证实，UA或UA联合沃拉替尼可降低Bcl-2、PLK1、p-AKT/AKT和p-mTOR/mTOR的水平，同时增加LC3 II/I。总之，该研究表明UA可能通过PLK1经由AKT/mTOR信号通路影响乳腺癌的细胞凋亡和自噬。
