Nrf2 induces cisplatin resistance through activation of autophagy in ovarian carcinoma.
Nrf2 induces cisplatin resistance through activation of autophagy in ovarian carcinoma.
复制标题
Nrf2 通过激活卵巢癌中的自噬诱导顺铂耐药。
DOI：
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发表时间：
2014-03
期刊：
影响因子：
--
通讯作者：
Yi, Xiao-Fang
中科院分区：
文献类型：
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作者：
Zheng, Yun-Xi;Yao, Ming;Zhang, Donna D;Yi, Xiao-Fang
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UNLABELLED
Cisplatin resistance is a major problem affecting ovarian carcinoma treatment. NF-E2-related factor 2 (Nrf2), a nuclear transcription factor, plays an important role in chemotherapy resistance. However, the underlying mechanism by which Nrf2 mediates cisplatin chemoresistance is unclear.
METHODS
The human ovarian carcinoma cell line, A2780, and its cisplatin-resistant variant, A2780cp were cultivated. Cell viability was determined with WST-8 assay. Western blot was applied to detect the expression of Nrf2, Nrf2 target genes, and autophagy-related proteins. RNA interference was used to knock down target genes. Annexin V and propidium iodide (PI) staining was utilized to quantify apoptosis. The ultrastructural analysis of autophagosomes was performed by transmission electron microscopy (TEM).
RESULTS
Nrf2 and its targeting genes, NQO1 and HO-1, are overexpressed in A2780cp cells compared with A2780 cells. Knocking down Nrf2 sensitized A2780cp cells to cisplatin treatment and decreased autophagy-related genes, Atg3, Atg6, Atg12 and p62 in both mRNA and protein levels. Furthermore, we demonstrated that in both cell lines cisplatin could induce the formation of autophagosomes and upregulate the expression of autophagy-related genes Atg3, Atg6 and Atg12. Treatment with an autophagy inhibitor, 3-Methyladenine (3-MA), or beclin 1 siRNA enhanced cisplatin-induced cell death in A2780cp cells, suggesting that inhibition of autophagy renders resistant cells to be more sensitive to cisplatin. Taken together, Nrf2 signaling may regulate cisplatin resistance by activating autophagy.
CONCLUSIONS
Nrf2-activated autophagy may function as a novel mechanism causing cisplatin-resistance.
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DOI：
10.5483/bmbrep.2004.37.2.139
发表时间：
2004-03
期刊：
Journal of biochemistry and molecular biology
影响因子：
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作者：
Jong‐Min Lee;Jeffrey A. Johnson
通讯作者：
Jong‐Min Lee;Jeffrey A. Johnson
DOI：
10.1360/032013-305
发表时间：
2014-03
期刊：
--
影响因子：
--
作者：
Zhaoyong Xi;Yangzhong Liu
通讯作者：
Zhaoyong Xi;Yangzhong Liu
影响因子：
5.3
作者：
Kim, Hak-Ryul;Kim, Sejin;Park, Raekil
通讯作者：
Park, Raekil
影响因子：
7.4
作者：
Stepkowski, Tomasz M.;Kruszewski, Marcin K.
通讯作者：
Kruszewski, Marcin K.
影响因子：
10.5
作者：
Itoh, K;Wakabayashi, N;Yamamoto, M
通讯作者：
Yamamoto, M