题名

新穎HDAC抑制劑在非小細胞肺癌之研究及建立TNBS誘導發炎性腸道疾病之動物模式

并列篇名

Effects of Novel HDAC Inhibitor on Non-Small Cell Lung Cancer and establishment of TNBS-induced acute colitis animal model

DOI

10.6342/NTU201602872

作者

邱安婕

关键词

TNBS ； IBD ； TKI resistance ； non-small cell lung cancer ； TNBS ； IBD ； TKI resistance ； non-small cell lung cancer

期刊名称

臺灣大學藥理學研究所學位論文

卷期/出版年月

2016年

学位类别

碩士
导师

陳青周
内容语文

繁體中文
中文摘要

第一代EGFR-TKI為activating mutation非小細胞肺癌病人之第一線用藥，治療約一年後會產生acquired resistance，因此發展第二及第三代藥物，然而抗藥性依舊會產生，因此探討EGFR-TKI抗藥性之機轉以克服抗藥性為重要之課題。 我們發現，HCC287/IR與H1975/AR皆具有mesenchymal form，伴隨E-cadherin之downregulation和Vimentin之upregulation，且H1975/AR細胞有Zeb1之upregulation；HCC287/IR與H1975/AR皆具較易形成spheroids，因此，EMT及癌幹細胞可能為EGFR-TKI抗藥性之主要原因。新穎HDAC抑制劑JMF3086在H1975/AR可抑制Zeb1之表現，增加E-cadherin及降低Vimentin之表現，對spheroids亦有相同之抑制作用。因此，JMF3086具潛力對抗EGFR-TKI之抗藥性。我們於RNA sequencing發現，HCC287/IR與H1975/AR皆有FoxC1之upregulation，可能亦與抗藥性和癌幹細胞之形成有關；JMF3086可抑制HCC287/IR與H1975/AR及spheroids之FoxC1表現，FoxC1可能可作為對抗非小細胞肺癌抗藥性之標的。 發炎性腸道疾病包括克隆氏症及潰瘍性結腸炎，目前未有治癒之藥物；TNBS誘導之急性大腸炎比擬人類之克隆氏症，本實驗中，新穎HDAC抑制劑JMF3086之salt form TWJ101，可預防TNBS造成之急性大腸炎，具開發為抗發炎藥物之潛力。
主题分类 醫藥衛生 > 藥理醫學
醫學院 > 藥理學研究所
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