CLC number:
On-line Access: 2021-06-11
Received: 2020-12-24
Revision Accepted: 2021-03-05
Crosschecked: 0000-00-00
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Citations: Bibtex RefMan EndNote GB/T7714
Xi WANG, Chunyan DAI, Yifei YIN, Lin WU, Weiyang JIN, Yufei FU, Zhe CHEN, Ke HAO, Bin LU. Blocking the JAK2/STAT3 and ERK pathways suppresses the proliferation of gastrointestinal cancers by inducing apoptosis[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2000842 @article{title="Blocking the JAK2/STAT3 and ERK pathways suppresses the proliferation of gastrointestinal cancers by inducing apoptosis", %0 Journal Article TY - JOUR
阻断JAK2/STAT3和ERK通路诱发凋亡抑制胃肠道癌的增殖创新点:发现JAK2/STAT3和ERK信号在胃癌(GC)和胰腺导管腺癌(PDAC)细胞内的相互作用,为克服胃肠道肿瘤的化疗耐药提供新的治疗策略。 方法:在GC和PDAC细胞系中,应用MEK抑制剂--曲美替尼(Trametinib)和JAK2抑制剂--费德拉替尼(Fedratinib)单独或共同抑制MEK和JAK2/STAT3信号通路,利用CCK-8和蛋白质印迹(western blot)方法检测细胞增殖和凋亡,及相关信号通路的激活情况;同时利用荷瘤小鼠检测JAK2/STAT3和MEK信号通路的抑制对肿瘤生长的影响。 结论:本研究发现,MEK抑制剂--曲美替尼在抑制MEK信号通路的同时却对JAK2/STAT3信号通路有较强的激活作用,无法有效抑制胃癌细胞和胰腺癌细胞的增殖;而JAK2抑制剂--费德拉替尼虽可以有效抑制JAK/STAT3信号通路的激活,但显著促进ERK信号通路的异常活化,导致对胃癌细胞和胰腺癌细胞的生长抑制作用失效。而当JAK2/STAT3和ERK信号通路同时被抑制后,抗增殖效果显著增强,且该作用效应与促进肿瘤细胞的凋亡进程密切相关。此外,这两种抑制剂的结合有效阻止了荷瘤小鼠的肿瘤生长,有很好的抗肿瘤效果,避免了化疗耐药的发生。 关键词组: Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article
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