胰腺癌
PAK1号
癌症研究
癌症
蛋白激酶B
激酶
体内
医学
癌细胞
细胞凋亡
恶性肿瘤
内科学
生物
生物化学
生物技术
作者
Weikang Kong,Lingxia Zhu,Tian Li,Jiao Chen,Bo Fan,Wenjing Ji,Chunli Zhang,Xueting Cai,Chunping Hu,Xiaoyan Sun,Peng Cao
标识
DOI:10.1016/j.ejphar.2023.175703
摘要
Pancreatic cancer is a lethal malignancy for which there is currently no effective treatment strategy. We previously reported that p21-activated kinase 1 (PAK1) is aberrantly expressed in pancreatic cancer patients and that targeted inhibition of PAK1 significantly suppressed pancreatic cancer progression in vitro and in vivo. In this study, we identified the drug azeliragon as a novel inhibitor of PAK1. Cell experiments revealed that azeliragon abolished PAK1 activation and promoted apoptosis in pancreatic cancer cells. Azeliragon was also found to significantly inhibit tumor growth in a pancreatic cancer xenograft model; when combined with afuresertib, an oral pan-AKT kinase inhibitor, azeliragon exhibited a strong synergistic effect against pancreatic cancer cells. Interestingly, afuresertib enhanced the antitumor efficacy of azeliragon in a xenograft mouse model. Collectively, our findings revealed previously unreported aspects of the drug azeliragon, and identified a novel combination strategy for the treatment of pancreatic cancer patients.
科研通智能强力驱动
Strongly Powered by AbleSci AI