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胰腺腺癌上调因子(PAUF)的抑制可增加胰腺癌对吉西他滨和5-氟尿嘧啶的敏感性,并抑制胰腺癌干细胞样细胞的形成。

Suppression of pancreatic adenocarcinoma upregulated factor (PAUF) increases the sensitivity of pancreatic cancer to gemcitabine and 5FU, and inhibits the formation of pancreatic cancer stem like cells.

作者信息

Cho Jae Hee, Kim Sun A, Park Soo Been, Kim Hee Man, Song Si Young

机构信息

Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.

Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea.

出版信息

Oncotarget. 2017 Jul 22;8(44):76398-76407. doi: 10.18632/oncotarget.19458. eCollection 2017 Sep 29.

DOI:10.18632/oncotarget.19458
PMID:29100320
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5652714/
Abstract

Pancreatic cancer stem cells (CSCs) play a crucial role in tumorigenesis and chemoresistance of pancreatic ductal adenocarcinoma. Pancreatic adenocarcinoma up-regulated factor (PAUF), a novel secretory protein, has been shown to contribute to cancer progression and metastasis. Because the clinical relationship between PAUF and pancreatic CSCs is largely unknown, we investigated the associations between the functional role of PAUF and pancreatic CSCs. Pancreatic cancer sphere cultured from the CFPAC-1 cells showed elevated expression of PAUF and pluripotent stemness genes (Oct4, Nanog, Stat3, and Sox2), and the mRNA of PAUF were increased in CD44CD24ESA pancreatic CSCs. PAUF knockdown (shPAUF) CFPAC-1 diminished the number of spheres and decreased stemness genes and CSC surface markers (CD133, c-MET and ALDH1). In addition, siPAUF CFPAC-1 decreased the mRNA expression of multidrug resistant protein 5 (MRP5) and ribonucleotide reductase M2 (RRM2) and were more vulnerable to gemcitabine and 5-FU than negative control (p<0.05). In conclusion, PAUF was increased in pancreatic CSCs and the suppression of PAUF enhances chemotherapeutic response to gemcitabine and 5FU by decreasing MRP5 and RRM2 in pancreatic cancer cells.

摘要

胰腺癌干细胞(CSCs)在胰腺导管腺癌的肿瘤发生和化疗耐药中起着关键作用。胰腺腺癌上调因子(PAUF)是一种新型分泌蛋白,已被证明有助于癌症进展和转移。由于PAUF与胰腺CSCs之间的临床关系很大程度上未知,我们研究了PAUF的功能作用与胰腺CSCs之间的关联。从CFPAC-1细胞培养的胰腺癌球显示PAUF和多能干性基因(Oct4、Nanog、Stat3和Sox2)表达升高,并且在CD44CD24ESA胰腺CSCs中PAUF的mRNA增加。PAUF敲低(shPAUF)的CFPAC-1减少了球的数量,并降低了干性基因和CSC表面标志物(CD133、c-MET和ALDH1)。此外,siPAUF CFPAC-1降低了多药耐药蛋白5(MRP5)和核糖核苷酸还原酶M2(RRM2)的mRNA表达,并且比阴性对照更易受吉西他滨和5-氟尿嘧啶的影响(p<0.05)。总之,PAUF在胰腺CSCs中增加,抑制PAUF可通过降低胰腺癌细胞中的MRP5和RRM2增强对吉西他滨和5-氟尿嘧啶的化疗反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1a0/5652714/19d86de407b5/oncotarget-08-76398-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1a0/5652714/44d23aafe162/oncotarget-08-76398-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1a0/5652714/96795adeab6f/oncotarget-08-76398-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1a0/5652714/b3b537072af0/oncotarget-08-76398-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1a0/5652714/19d86de407b5/oncotarget-08-76398-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1a0/5652714/44d23aafe162/oncotarget-08-76398-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1a0/5652714/96795adeab6f/oncotarget-08-76398-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1a0/5652714/b3b537072af0/oncotarget-08-76398-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1a0/5652714/19d86de407b5/oncotarget-08-76398-g004.jpg

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