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防己诺林碱通过抑制 PI3K/Akt/XIAP 轴诱导胆囊癌细胞凋亡。

Fangchinoline induces gallbladder cancer cell apoptosis by suppressing PI3K/Akt/XIAP axis.

机构信息

Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Department of Hepatobiliary Surgery, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, Zhejiang, China.

出版信息

PLoS One. 2022 Apr 21;17(4):e0266738. doi: 10.1371/journal.pone.0266738. eCollection 2022.

Abstract

Gallbladder cancer (GBC) is the most common biliary tract malignancy with a dismal prognosis. The development of new drugs may help to improve prognosis. This study found that fangchinoline, a bisbenzylisoquinoline alkaloids, inhibited the proliferation and clone formation of GBC cells in a dose-dependent manner. Moreover, Hoechst staining, TUNEL assays, and flow cytometry demonstrated that fangchinoline effectively induced apoptosis in GBC cells. Further studies found that an anti-apoptotic pathway, the PI3K/Akt/XIAP axis, was significantly inhibited in GBC cells after treating with fangchinoline. Finally, we confirmed that fangchinoline restrained xenograft tumor growth in vivo. Our findings indicate that fangchinoline can be considered a potential drug for GBC treatment.

摘要

胆囊癌(GBC)是最常见的胆道恶性肿瘤,预后不良。开发新的药物可能有助于改善预后。本研究发现,蝙蝠葛碱,一种双苄基异喹啉生物碱,以剂量依赖的方式抑制 GBC 细胞的增殖和克隆形成。此外,Hoechst 染色、TUNEL 检测和流式细胞术表明,蝙蝠葛碱能有效诱导 GBC 细胞凋亡。进一步的研究发现,在 GBC 细胞中,抗凋亡途径,PI3K/Akt/XIAP 轴,在蝙蝠葛碱处理后被显著抑制。最后,我们证实蝙蝠葛碱能抑制体内异种移植瘤的生长。我们的研究结果表明,蝙蝠葛碱可被视为治疗 GBC 的一种潜在药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e738/9022853/14c25e298122/pone.0266738.g001.jpg

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