Chen Lu, Xia Yuting, Min Liangliang, Zhang Yuqin, Huang Da, Zhang Yulu, You Aihua, Li Zhihua
Jiangxi Provincial Key Laboratory of Breast Diseases (No.2024SSY06221), Nanchang People's Hospital, Nanchang, China.
Sichuan Tianfu New Area Wan'an Community Health Center, Sichuan, China.
Pharm Biol. 2025 Dec;63(1):503-523. doi: 10.1080/13880209.2025.2537123. Epub 2025 Jul 24.
Sophoridine, an alkaloid quinolizidine derived from Aiton (Fabaceae), has strong anti-tumor activity in a variety of malignancies. Nevertheless, the effects and underlying mechanism of sophoridine on breast cancer are not fully understood.
To identify the key targets and potential pharmacological mechanisms of sophoridine against breast cancer.
MCF-10A, MCF-7 and MDA-MB-231 cells were treated with sophoridine for 24 or 48 h. MTT, colony formation assay, flow cytometry, wound healing, and Transwell assay were employed to illustrate the anti-tumor effects of sophoridine on breast cancer. Network pharmacology and molecular docking were used to determine the targets for sophoridine in breast cancer, and confirmed by molecular dynamics simulation and CETSA-western blot assay. Additionally, the functional rescue and signaling pathway regulated by sophoridine was analyzed.
Sophoridine suppressed the proliferation, migration, and invasion of breast cancer cells. The IC value of sophoridine for 48 h in MCF-10A, MCF-7 and MDA-MB-231 was 363 μM, 87.96 μM and 81.07 μM, respectively. PIM1 was the key target for sophoridine in breast cancer. Furthermore, PIM1 overexpression significantly reversed the suppressive impacts of sophoridine on growth and migration in breast cancer cells. Mechanistically, sophoridine inhibited the phosphorylation of ASK1 and activated JNK/p38 MAPK signaling pathway by downregulating PIM1 expression, and thus exhibited anti-tumor effects.
Taken together, sophoridine relies on targeting PIM1 to inhibit cell proliferation and migration in breast cancer, which might be related to the activation of ASK1/MAPK axis, suggesting the therapeutic potential of sophoridine for breast cancer.
槐定碱是一种从鹰爪豆（豆科）中提取的喹诺里西啶生物碱，在多种恶性肿瘤中具有很强的抗肿瘤活性。然而，槐定碱对乳腺癌的作用及其潜在机制尚未完全明确。
确定槐定碱抗乳腺癌的关键靶点和潜在药理机制。
用槐定碱处理MCF-10A、MCF-7和MDA-MB-231细胞24或48小时。采用MTT法、集落形成试验、流式细胞术、伤口愈合试验和Transwell试验来说明槐定碱对乳腺癌的抗肿瘤作用。利用网络药理学和分子对接确定槐定碱在乳腺癌中的靶点，并通过分子动力学模拟和CETSA-蛋白质免疫印迹分析进行验证。此外，还分析了槐定碱调节的功能拯救和信号通路。
槐定碱抑制乳腺癌细胞的增殖、迁移和侵袭。槐定碱作用48小时时，在MCF-10A、MCF-7和MDA-MB-231细胞中的半数抑制浓度分别为363μM、87.96μM和81.07μM。PIM1是槐定碱在乳腺癌中的关键靶点。此外，PIM1过表达显著逆转了槐定碱对乳腺癌细胞生长和迁移的抑制作用。机制上，槐定碱通过下调PIM1表达抑制ASK1的磷酸化并激活JNK/p38 MAPK信号通路，从而发挥抗肿瘤作用。
综上所述，槐定碱通过靶向PIM1抑制乳腺癌细胞增殖和迁移，这可能与ASK1/MAPK轴的激活有关；提示槐定碱在乳腺癌治疗中具有潜在应用价值。
