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Cordycepin inhibits pancreatic cancer cell growth in vitro and in vivo via targeting FGFR2 and blocking ERK signaling

文献类型: 外文期刊

作者: Li Xue-Ying 1 ; Tao Hong 1 ; Jin Can 1 ; Du Zhen-Yun 1 ; Liao Wen-Feng 1 ; Tang Qing-Jiu 4 ; Ding Kan 1 ;

作者机构: 1.Chinese Acad Sci, Glycochemistry & Glycobiol Lab, Key Lab Receptor Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China

2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China

3.Nanchang Univ, Coll Pharm, Nanchang 330006, Jiangxi, Peoples R China

4.Shanghai Acad Agr Sci, Inst Edible Fungi, Shanghai 201203, Peoples R China

关键词: Cordycepin; FGFR2; Apoptosis; Pancreatic cancer; Ras/Erk

期刊名称:CHINESE JOURNAL OF NATURAL MEDICINES ( 影响因子:3.0; 五年影响因子:2.869 )

ISSN: 2095-6975

年卷期: 2020 年 18 卷 5 期

页码:

收录情况: SCI

摘要: Cordycepin (3'-deoxyadenosine) from Cordyceps militaris has been reported to have anti-tumor effects. However, the molecular target and mechanism underlying cordycepin impeding pancreatic cancer cell growth in vitro and in vivo remain vague. In this study, we reported functional target molecule of cordycepin which inhibited pancreatic cancer cells growth in vitro and in vivo. Cordycepin was confirmed to induce apoptosis by activating caspase-3, caspase-9 and cytochrome c. Further studies suggested that MAPK pathway was blocked by cordycepin via inhibiting the expression of Ras and the phosphorylation of Erk. Moreover, cordycepin caused S-phase arrest and DNA damage associated with activating Chk2 (checkpoint kinase 2) pathway and downregulating cyclin A2 and CDK2 phosphorylation. Very interestingly, we showed that cordycepin could bind to FGFR2 (K-D = 7.77 x 10(-9)) very potently to inhibit pancreatic cancer cells growth by blocking Ras/ErK pathway. These results suggest that cordycepin could potentially be a leading compound which targeted FGFR2 to inhibit pancreatic cells growth by inducing cell apoptosis and causing cell cycle arrest via blocking FGFR/Ras/ERK signaling for anti-pancreatic cancer new drug development.

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