PI3K/AKT/mTOR通路
蛋白激酶B
化学
LY294002型
细胞凋亡
碘化丙啶
药理学
癌症研究
内分泌学
内科学
生物
医学
生物化学
程序性细胞死亡
作者
Yanxiong Shao,Jiayao Fu,Tianle Zhan,Lei Ye,Chuangqi Yu
出处
期刊:Current Molecular Pharmacology
[Bentham Science]
日期:2022-02-17
卷期号:15 (7): 969-979
被引量:2
标识
DOI:10.2174/1874467215666220217103233
摘要
Fangchinoline is a bisbenzylisoquinoline alkaloid extracted from Stephania tetrandra S. Moore that is conventionally used as an analgesic, antirheumatic, and antihypertensive drug in China. However, the application of Fanchinoline in Sjögren syndrome (SS) remains unreported.This study aimed to identify the potential role of Fangchinoline in the treatment of SS via altering Akt/mTOR signaling.First, we examined levels of p-Akt and p-mTOR in infiltrating lymphocytes of labial glands from SS patients by immunohistochemistry. Then, the effects of Fangchinoline on Raji cells and Daudi cells were investigated using the CCK-8 assay, propidium iodide (PI)/RNase, and Annexin V/PI staining. Western blotting was used to identify the levels of Akt, p-Akt(ser473), mTOR, and p-mTOR. For in vivo analyses, NOD/Ltj and wild-type ICR mice were treated with a Fangchinoline solution, an LY294002 solution (an inhibitor of the PI3K/Akt/mTOR pathway), or their solvent for 28 days. Then, salivary flow assays and hematoxylin and eosin staining of submandibular glands were performed to determine the severity of SS-like responses in the mice.Immunohistochemical staining of labial glands from SS patients showed that activation of p-Akt and p-mTOR in infiltrating lymphocytes might be correlated with SS development. In vitro, Fangchinoline and LY294002 inhibited proliferation, induced cell cycle arrest, and promoted apoptosis in Raji and Daudi cells by altering Akt/mTOR signaling. In vivo, Fangchinoline and LY294002 significantly improved the salivary secretion by NOD/Ltj mice and reduced the number of lymphocytic foci in the submandibular glands.These results indicated that Fangchinoline could effectively inhibit the proliferation of neoplastic B-lymphoid cells and reduce SS-like responses in NOD/Ltj mice. Our study highlights the potential value of the clinical application of Fangchinoline for SS treatment.
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