癌症研究
胰腺癌
细胞凋亡
体内
PI3K/AKT/mTOR通路
医学
恶性肿瘤
体外
细胞生长
癌症
蛋白激酶B
药理学
内科学
生物
生物化学
遗传学
生物技术
作者
Zhijian Ma,Qianlin Gu,Yinmei Dai,Qiaoyan Wang,Wei Shi,Jiao Zhang
摘要
Abstract Pancreatic cancer (PC) is a highly aggressive and deadly malignancy with limited treatment options and poor prognosis. Identifying new therapeutic targets and developing effective strategies for PC treatment is of utmost importance. Here, we revealed that SHCBP1 is significantly overexpressed in PC and negatively correlated with patient prognosis. Knockout of SHCBP1 inhibits the proliferation and migration of PC cells in vitro, and suppresses the tumor growth in vivo. In addition, we identified AZD5582 as a novel inhibitor of SHCBP1, which efficiently restrains the growth of PC in cell lines, organoids, and patient‐derived xenografts. Mechanistically, we found that AZD5582 induced the apoptosis of PC cells by inhibiting the activity of PI3K/AKT signaling and preventing the degradation of TP53. Collectively, our study highlights SHCBP1 as a potential therapeutic target and its inhibitor AZD5582 as a viable agent for PC treatment strategies.
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