Depleted aldehyde dehydrogenase 1A1 (ALDH1A1) reverses cisplatin resistance of human lung adenocarcinoma cell A549/DDP.
Depleted aldehyde dehydrogenase 1A1 (ALDH1A1) reverses cisplatin resistance of human lung adenocarcinoma cell A549/DDP.
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耗尽的乙醛脱氢酶 1A1 (ALDH1A1) 逆转人肺腺癌细胞 A549/DDP 的顺铂耐药性
DOI：
10.1111/1759-7714.12400
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发表时间：
2017-01
期刊：
影响因子：
2.9
通讯作者：
Wu J
中科院分区：
文献类型：
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作者：
Wei Y;Wu S;Xu W;Liang Y;Li Y;Zhao W;Wu J
Cisplatin is the standard first‐line chemotherapeutic agent for the treatment of non‐small cell lung cancer (NSCLC). However, resistance to chemotherapy has been a major obstacle in the management of NSCLC. Aldehyde dehydrogenase 1A1 (ALDH1A1) overexpression has been observed in a variety of cancers, including lung cancer. The purpose of this study was to investigate the effect of ALDH1A1 expression on cisplatin resistance and explore the mechanism responsible. Reverse transcriptase‐PCR was applied to measure the messenger RNA expression of ALDH1A1, while Western blot assay was employed to evaluate the protein expression of ALDH1A1, B‐cell lymphoma 2, Bcl‐2‐like protein 4, phospho‐protein kinase B (p‐AKT) and AKT. A short hairpin RNA was used to knockdown ALDH1A1 expression. A 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay was used to determine the effect of ALDH1A1 decrease on cell viability. The cell apoptotic rate was tested using flow cytometry assay. ALDH1A1 is overexpressed in cisplatin resistant cell line A549/DDP, compared with A549. ALDH1A1 depletion significantly decreased A549/DDP proliferation, increased apoptosis, and reduced cisplatin resistance. In addition, the phosphoinositide 3‐kinase (PI3K) / AKT pathway is activated in A549/DDP, and ALDH1A1 knockdown reduced the phosphorylation level of AKT. Moreover, the combination of ALDH1A1‐short hairpin RNA and PI3K/AKT pathway inhibitor LY294002 markedly inhibited cell viability, enhanced apoptotic cell death, and increased cisplatin sensitivity. These results suggest that ALDH1A1 depletion could reverse cisplatin resistance in human lung cancer cell line A549/DDP, and may act as a potential target for the treatment of lung cancers resistant to cisplatin.
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影响因子：
3.8
作者：
Li XS;Xu Q;Fu XY;Luo WS
通讯作者：
Luo WS
影响因子：
3
作者：
Moreb, Jan S.;Muhoczy, Dagmara;Zucali, James R.
通讯作者：
Zucali, James R.
影响因子：
4.2
作者：
Sun, Mingli;Zhao, Haishan;Wei, Minjie
通讯作者：
Wei, Minjie
影响因子：
8
作者：
通讯作者：
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DOI：
10.1038/modpathol.2011.172
发表时间：
2012-03
期刊：
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
影响因子：
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作者：
通讯作者：
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