Nuclear factor (erythroid-derived 2)-like 2 regulates drug resistance in pancreatic cancer cells.
Nuclear factor (erythroid-derived 2)-like 2 regulates drug resistance in pancreatic cancer cells.
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DOI：
10.1097/mpa.0b013e3181c31314
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发表时间：
2010-05
期刊：
影响因子：
2.9
通讯作者：
Bae I
中科院分区：
文献类型：
--
作者：
Hong YB;Kang HJ;Kwon SY;Kim HJ;Kwon KY;Cho CH;Lee JM;Kallakury BV;Bae I
探讨胰腺癌耐药的分子基础。分析Nrf2在胰腺癌组织和细胞系中的表达水平。Nrf2激活和耐药性之间的临床相关性通过测量Nrf2和ABCG 2通过这些基因的过表达或敲低调节后的细胞活力来证明。通过Hoechst 33342染色测量ABCG 2的活性。相对于正常胰腺组织，在胰腺癌组织和细胞系中观察到异常升高的Nrf2蛋白水平。通过外源Nrf2的过表达或通过激活内源Nrf2来增加Nrf2蛋白水平导致耐药性增加。相反，内源性Nrf2蛋白水平的降低或内源性Nrf2的失活导致耐药性降低。耐药或敏感性的这些变化也与Nrf2下游基因的表达水平呈正相关。ABCG 2的表达与耐药相关。由于胰腺癌的内在耐药性部分是由于Nrf2蛋白水平异常升高，因此对调节Nrf2活性的进一步研究可能会导致开发新的胰腺癌治疗方法。
To investigate the molecular basis of drug resistance in pancreatic cancer. The expression of Nrf2 levels in pancreatic cancer tissues and cell lines was analyzed. Clinical relevance between Nrf2 activation and drug resistance was demonstrated by measuring cell viability after Nrf2 and ABCG2 regulation by over-expression or knockdown of these genes. Activity of ABCG2 was measured by Hoechst 33342 staining. Abnormally elevated Nrf2 protein levels were observed in pancreatic cancer tissues and cell lines relative to normal pancreatic tissues. Increasing Nrf2 protein levels either by over-expression of exogenous Nrf2 or by activating endogenous Nrf2 resulted in increased drug resistance. Conversely, a reduction in endogenous Nrf2 protein levels or inactivation of endogenous Nrf2 resulted in decreased drug resistance. These changes in drug resistance or sensitivity were also positively correlated to the expression levels of Nrf2 downstream genes. Similarly, the expression of ABCG2 was correlated with drug resistance. Since the intrinsic drug resistance of pancreatic cancers is, in part, due to abnormally elevated Nrf2 protein levels, further research on regulating Nrf2 activity may result in the development of novel pancreatic cancer therapies.