Abstract
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.