NOS1 upregulates ABCG2 expression contributing to DDP chemoresistance in ovarian cancer cells
NOS1 upregulates ABCG2 expression contributing to DDP chemoresistance in ovarian cancer cells
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NOS1上调ABCG2表达导致卵巢癌细胞中DDP化疗耐药
DOI：
10.3892/ol.2018.9787
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发表时间：
2019-02-01
期刊：
影响因子：
2.9
通讯作者：
Wang, Yifeng
中科院分区：
文献类型：
--
作者：
Li, Xiaoxuan;Zou, Zhiwei;Wang, Yifeng
据报道，一氧化氮合酶1（NOS 1）促进各种癌症过程，包括化学抗性。然而，NOS 1在化疗耐药性中的作用仍不清楚。ATP结合盒，亚家族G，成员2（ABCG 2）已被确定为多种癌症类型（包括卵巢癌）的多药耐药的分子原因。本研究观察到在卵巢癌细胞中，ABCG 2的表达在顺铂/顺铂（cisplatin/DDP）处理的反应中显著上调，此外NOS 1的表达呈现增加的趋势。此外，基因表达Omnibus数据集（GSE 26712和GSE 51373）中化疗耐药卵巢癌谱中的NOS 1和ABCG 2水平高于化疗敏感谱。NOS 1过表达可上调ABCG 2的表达，NOS 1选择性抑制剂（N-PLA）可抑制ABCG 2的表达。在细胞存活测定中，NOS 1似乎增加了DDP耐药的可能性，并且这种作用可通过添加ABCG 2抑制剂（维拉帕米）逆转。本研究表明，NOS 1诱导的化疗耐药性部分是通过上调ABCG 2表达介导的。这一结果提示卵巢癌中NOS 1的表达与ABCG 2相关的化疗耐药性之间存在联系。
Nitric oxide synthase 1 (NOS1) has been reported to promote various cancer processes including chemoresistance. However, the role of NOS1 in chemoresistance has remained unclear. ATP-binding cassette, subfamily G, member 2 (ABCG2) has been identified as a molecular cause of multidrug resistance in a number of cancer types, including ovarian cancer. The present study observed that in ovarian cancer cells, the expression of ABCG2 was significantly upregulated in response to cis-diamminedichloroplatinum (cisplatin/DDP) treatment, in addition the expression of NOS1 exhibited an increasing trend. Additionally, the levels of NOS1 and ABCG2 in chemoresistant ovarian cancer profiles in Gene Expression Omnibus datasets (GSE26712 and GSE51373) were higher than in chemosensitive profiles. Furthermore, overexpression of NOS1 could upregulate ABCG2 expression, and expression of ABCG2 was inhibited by NOS1 selective inhibitor (N-PLA). In assays of cell survival, NOS1 appeared to increase the potential for DDP resistance, and this effect was reversed by addition of ABCG2 inhibitor (verapamil). The present study indicated that NOS1-induced chemoresistance was partly mediated by the upregulation of ABCG2 expression. This result suggests a link between the expression of NOS1 and the ABCG2-associated chemoresistance in ovarian cancer.