胆囊癌（GBC）是胆道系统常见的恶性肿瘤，严重威胁人类健康。探索治疗GBC的理想药物刻不容缓。苦参碱是苦参的主要活性成分，具有抗炎、抗病毒、免疫调节、抗肿瘤等广泛的生物活性。然而，苦参碱治疗 GBC 的潜在机制仍不清楚。本研究的目的是在体内和体外研究苦参碱对 GBC 的抗肿瘤作用，并阐明其潜在的调节机制。在这里，我们通过CCK8和流式细胞术发现苦参碱对GBC具有显着的杀伤作用，包括细胞周期阻滞、抑制GBC细胞和诱导细胞凋亡。进一步的体内研究证实了苦参碱对 NOZ 异种移植裸鼠肿瘤生长的抑制作用。同时，通过划痕和Transwell实验，苦参碱还显着抑制GBC细胞的迁移和侵袭。此外，通过检测上皮间质转化（EMT）和基质金属蛋白酶的mRNA和蛋白水平，进一步证实了苦参碱对GBC侵袭和迁移的抑制作用。从机制角度来看，网络药理学分析表明苦参碱治疗GBC的潜在靶点富含PI3K/AKT信号通路。随后，苦参碱有效降低体内和体外p-PI3K和p-AKT蛋白的丰度。更重要的是，PI3K激活剂(740 Y-P)拮抗苦参碱的抗肿瘤作用，而PI3K抑制剂(LY294002)则增加苦参碱对GBC的敏感性。基于以上研究结果，我们得出结论：苦参碱通过调节PI3K/AKT信号通路抑制GBC的侵袭和迁移。我们的研究结果表明了苦参碱在抑制GBC生长中的关键作用和调节机制，这为苦参碱成为GBC治疗和研究的候选药物提供了理论基础。© 2024。作者，独家许可施普林格自然出版社德国施普林格出版社。

Gallbladder cancer (GBC) is a common malignant cancer in the biliary system, which poses a serious threat to human health. It is urgent to explore ideal drugs for the treatment of GBC. Matrine is the main active ingredient of Sophora flavescentis, with a wide range of biological activities encompassing anti-inflammatory, antiviral, immunomodulatory, and anti-tumor. However, the underlying mechanism by which Matrine treats GBC is still unclear. The purpose of this study is to investigate the anti-tumor effects of Matrine on GBC in vivo and in vitro and to clarify the potential regulatory mechanisms. Here, we found that Matrine had a significant killing effect on GBC through CCK8 and flow cytometry, including arrest of cell cycle, inhibition of GBC cell, and induction of apoptosis. Further in vivo studies confirmed the inhibitory effect of Matrine on tumor growth in NOZ xenografted nude mouse. At the same time, Matrine also significantly suppressed the migration and invasion of GBC cells through scratch and Transwell experiments. In addition, by detecting the mRNA and protein levels of epithelial-mesenchymal transition (EMT) and matrix metalloproteinases, Matrine furtherly substantiated the inhibitory role on invasion and migration of GBC. From a mechanistic perspective, network pharmacology analysis suggests that the potential targets of Matrine in the treatment of GBC are enriched in the PI3K/AKT signaling pathway. Subsequently, Matrine effectively decreased the abundance of p-PI3K and p-AKT protein in vivo and in vitro. More importantly, PI3K activator (740 Y-P) antagonized the anti-tumor effect of Matrine, while PI3K inhibitor (LY294002) increased the sensitivity of Matrine for GBC. Based on the above findings, we conclude that Matrine inhibits the invasion and migration of GBC by regulating PI3K/AKT signaling pathway. Our results indicate the crucial role and regulatory mechanism of Matrine in suppressing the growth of GBC, which provides a theoretical basis for Matrine to be a candidate drug for the treatment and research of GBC.© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.