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利德内酯通过负调控PI3K/AKT信号通路抑制胰腺癌的发展。

Linderalactone Suppresses Pancreatic Cancer Development and via Negatively Regulating PI3K/AKT Signaling Pathway.

作者信息

Xu Dongchao, Tian Mengyao, Chen Wangyang, Bian Ying, Xia Xiaofeng, Liu Qiang, Zheng Liyun, Zhang Xiaofeng, Shen Hongzhang

机构信息

Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China.

Hangzhou Institute of Digestive Diseases, Hangzhou 310000, China.

出版信息

J Oncol. 2022 Aug 4;2022:8675096. doi: 10.1155/2022/8675096. eCollection 2022.

Abstract

Linderalactone is one of the main extracts of Linderae Radix, which is widely used in traditional Chinese medicine. There have been few studies on the antitumor effect of linderalactone in the past. In this study, we explored the anti-pancreatic cancer activity of linderalactone and . The  results showed that linderalactone inhibited the proliferation of pancreatic cancer cells in a time- and dose-dependent manner. Cell migration and invasion were significantly inhibited by linderalactone. The cell cycle was arrested in the G2/M phase, and the expression levels of cell cycle-associated proteins changed significantly with linderalactone treatment. In addition, linderalactone induced cell apoptosis and altered the expression of apoptotic markers, such as caspase 3 and PARP1. Mechanistically, linderalactone suppressed the PI3K/AKT  signaling pathway by downregulating the phosphorylation of PI3K and AKT. The xenograft study results were consistent with the results, and there was no obvious chemical toxicity. Thus, our research demonstrated that linderalactone exhibits antitumor activity against pancreatic cancer and may be developed as a potential anti-pancreatic cancer agent in the future.

摘要

乌药内酯是乌药的主要提取物之一,在传统中药中广泛应用。过去关于乌药内酯抗肿瘤作用的研究较少。在本研究中,我们探究了乌药内酯的抗胰腺癌活性。结果表明,乌药内酯以时间和剂量依赖性方式抑制胰腺癌细胞的增殖。乌药内酯显著抑制细胞迁移和侵袭。细胞周期阻滞于G2/M期,且细胞周期相关蛋白的表达水平随乌药内酯处理发生显著变化。此外,乌药内酯诱导细胞凋亡并改变凋亡标志物如半胱天冬酶3和聚(ADP-核糖)聚合酶1的表达。机制上,乌药内酯通过下调磷脂酰肌醇-3-激酶(PI3K)和蛋白激酶B(AKT)的磷酸化来抑制PI3K/AKT信号通路。异种移植研究结果与上述结果一致,且无明显化学毒性。因此,我们的研究表明乌药内酯对胰腺癌具有抗肿瘤活性,未来可能被开发成为一种潜在的抗胰腺癌药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a36/9371883/c67d7943991b/JO2022-8675096.001.jpg

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