Inhibition of pancreatic cancer Panc1 cell migration by omeprazole is dependent on aryl hydrocarbon receptor activation of JNK.
Inhibition of pancreatic cancer Panc1 cell migration by omeprazole is dependent on aryl hydrocarbon receptor activation of JNK.
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DOI：
10.1016/j.bbrc.2018.05.061
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发表时间：
2018-06-27
影响因子：
3.1
通讯作者：
Safe S
中科院分区：
文献类型：
--
作者：
Jin UH;Karki K;Kim SB;Safe S
筛选了几种芳香烃受体（AhR）活性药物作为胰腺癌细胞侵袭的抑制剂，并确定了两种抑制侵袭的化合物奥美拉唑。奥美拉唑对高度侵袭性Panc 1细胞侵袭的抑制涉及AhR依赖性非基因组途径，奥美拉唑介导的Panc 1细胞侵袭抑制依赖于Jun-N-末端激酶（JNK）和丝裂原活化激酶激酶7（MKK 7）。奥美拉唑未能诱导AhR核转位不是由于胞浆AhR伴侣蛋白Hsp 90或XAP 2的过表达，DNA测序结果表明，在Panc 1细胞中表达的AhR没有突变。RNAseq研究的结果表明，奥美拉唑诱导了几种促侵袭因子的AhR依赖性下调，包括活化的白细胞粘附分子（ALCAM），长链脂肪酸CoA合酶（CSL 4），stathmin 3（STMN 3）和neuropillin 2（NRP 2），目前正在研究这些基因的具体功能。
Several aryl hydrocarbon receptor (AhR)-active pharmaceuticals were screened as inhibitors of pancreatic cancer cell invasion and identified two compounds, omeprazole, that inhibited invasion. Inhibition of highly invasive Panc1 cell invasion by omeprazole involves an AhR-dependent non-genomic pathway, and omeprazole-mediated inhibition of Panc1 cell invasion was dependent on Jun-N-terminal kinase (JNK) and mitogen-activated kinase kinase 7 (MKK7). The failure of omeprazole to induce nuclear translocation of the AhR was not due to overexpression of cytosolic AhR partner proteins Hsp90 or XAP2, and results of DNA sequencing show that the AhR expressed in Panc1 cells was not mutated. Results of RNAseq studies indicate that omeprazole induced an AhR-dependent downregulation of several pro-invasion factors including activated leukocyte cell adhesion molecule (ALCAM), long chain fatty acid CoA-synthase (CSL4), stathmin 3 (STMN3) and neuropillin 2 (NRP2), and the specific functions of these genes are currently being investigated.
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影响因子：
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