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对胰腺癌细胞系的抗增殖和凋亡作用表明血管生成素样蛋白8(Betatrophin)具有新的作用。

Anti proliferative and apoptotic effects on pancreatic cancer cell lines indicate new roles for ANGPTL8 (Betatrophin).

作者信息

Taherkhani Fatemeh, Hosseini Kamran Mousavi, Zebardast Sanaz, Chegini Koorosh Goodarzvand, Gheibi Nematollah

机构信息

Iranian Blood Transfusion Organization, Research Center, Tehran, Iran.

Cellular and Molecular Research Center, Research Institute for Prevention of Non-Communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran.

出版信息

Genet Mol Biol. 2020 Jul 31;43(3):e20190196. doi: 10.1590/1678-4685-GMB-2019-0196.

DOI:10.1590/1678-4685-GMB-2019-0196
PMID:32745158
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7416753/
Abstract

Despite considerable advances, the treatment of pancreatic cancer (PC) still requires much effort. Unusual regulation of the Wnt and apoptotic signaling pathways is widespread in cancer incidence. For instance, the WIF1 (Wnt inhibitory factor 1) gene is down-regulated in many cancers. The purpose of this study was to determine the effects of recombinant Betatrophin, a recently discovered hormone, on MiaPaca-II and Panc-1 pancreatic cell lines. Various concentrations of Betatrophin were added to MiaPaca-II and Panc-1 pancreatic cell lines during periods of 24 , 48, and 72 h. The MTT assay was applied to investigate cell proliferation after treatment. The rate of apoptotic cells was assessed using double-staining flow cytometry, and the expression levels of the WIF1 gene and Bcl2 protein was observed by real-time PCR and western blotting, respectively. The findings of this study suggest that Betatrophin has an anti-proliferative effect on both MiaPaca-II and Panc-1 cell lines, in line with the up-regulation of WIF1 as a tumor suppressor gene. Moreover, the induction of apoptosis by ANGPTL8 occurred by the down-regulation of Bcl2. Thus, Betatrophin can be proposed as a potential therapeutic drug for treating pancreatic cancer.

摘要

尽管取得了显著进展,但胰腺癌(PC)的治疗仍需付出很多努力。Wnt和凋亡信号通路的异常调控在癌症发生中很普遍。例如,WIF1(Wnt抑制因子1)基因在许多癌症中表达下调。本研究的目的是确定重组Betatrophin(一种最近发现的激素)对MiaPaca-II和Panc-1胰腺癌细胞系的影响。在24、48和72小时期间,将不同浓度的Betatrophin添加到MiaPaca-II和Panc-1胰腺癌细胞系中。采用MTT法检测处理后细胞的增殖情况。使用双染流式细胞术评估凋亡细胞率,分别通过实时PCR和蛋白质印迹法观察WIF1基因和Bcl2蛋白的表达水平。本研究结果表明,Betatrophin对MiaPaca-II和Panc-1细胞系均具有抗增殖作用,这与作为肿瘤抑制基因的WIF1上调一致。此外,ANGPTL8通过下调Bcl2诱导细胞凋亡。因此,Betatrophin可被认为是一种治疗胰腺癌的潜在治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/625e/7416753/f1ae1a7979a9/1415-4757-GMB-43-3-e20190196-gf05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/625e/7416753/5a6a7245e5aa/1415-4757-GMB-43-3-e20190196-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/625e/7416753/0ae2b3db09e3/1415-4757-GMB-43-3-e20190196-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/625e/7416753/10b9bdfff4a7/1415-4757-GMB-43-3-e20190196-gf03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/625e/7416753/7530b806c65f/1415-4757-GMB-43-3-e20190196-gf04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/625e/7416753/f1ae1a7979a9/1415-4757-GMB-43-3-e20190196-gf05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/625e/7416753/5a6a7245e5aa/1415-4757-GMB-43-3-e20190196-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/625e/7416753/0ae2b3db09e3/1415-4757-GMB-43-3-e20190196-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/625e/7416753/10b9bdfff4a7/1415-4757-GMB-43-3-e20190196-gf03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/625e/7416753/7530b806c65f/1415-4757-GMB-43-3-e20190196-gf04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/625e/7416753/f1ae1a7979a9/1415-4757-GMB-43-3-e20190196-gf05.jpg

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本文引用的文献

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Cloning, expression, and spectral analysis of mouse betatrophin.小鼠β-促胰岛素分泌素的克隆、表达及光谱分析
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CDK3, target of miR-4469, suppresses breast cancer metastasis inhibiting Wnt/β-catenin pathway.CDK3作为miR-4469的靶点,通过抑制Wnt/β-连环蛋白信号通路来抑制乳腺癌转移。
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