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NOS1 upregulates ABCG2 expression contributing to DDP chemoresistance in ovarian cancer cells

Xiaoxuan Li1, Zhiwei Zou2, Jiao Tang1

  • 1Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, P.R. China.

Oncology Letters
|January 25, 2019
PubMed

Insights

Nitric oxide synthase 1 (NOS1) promotes ovarian cancer chemoresistance by upregulating ABCG2. Inhibiting NOS1 or ABCG2 can reverse this resistance, offering potential therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Nitric oxide synthase 1 (NOS1) is implicated in cancer progression and chemoresistance.
  • ATP-binding cassette, subfamily G, member 2 (ABCG2) is a known driver of multidrug resistance, particularly in ovarian cancer.

Purpose of the Study:

  • To investigate the role of NOS1 in chemoresistance in ovarian cancer.
  • To determine the relationship between NOS1 and ABCG2 expression in cisplatin-resistant ovarian cancer.

Main Methods:

  • Ovarian cancer cells were treated with cisplatin (DDP).
  • Expression levels of NOS1 and ABCG2 were analyzed using cell culture and Gene Expression Omnibus datasets (GSE26712, GSE51373).
  • Functional assays involved NOS1 overexpression, NOS1 inhibition (N-PLA), and ABCG2 inhibition (verapamil).

Main Results:

  • Cisplatin treatment upregulated both NOS1 and ABCG2 expression in ovarian cancer cells.
  • Higher NOS1 and ABCG2 levels were observed in chemoresistant ovarian cancer profiles.
  • NOS1 overexpression increased ABCG2 expression, while NOS1 inhibition decreased it.
  • NOS1 enhanced DDP resistance, an effect reversed by ABCG2 inhibition.

Conclusions:

  • NOS1 contributes to chemoresistance in ovarian cancer, partly through the upregulation of ABCG2.
  • The NOS1-ABCG2 pathway represents a potential therapeutic target for overcoming chemoresistance in ovarian cancer.
Keywords:
ATP-binding cassettechemoresistancecis-diamminedichloroplatinummember 2nitric oxide synthase 1ovarian cancersubfamily G

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