Affiliation:
1. Department of Gynecology, School of Medicine, The Second Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang,
310009, China
Abstract
Background::
Chemoresistance is a major cause of relapse or death in ovarian cancer (OC) patients.
New evidence suggests the crucial role of myeloid-derived suppressor cells (MDSCs) in mediating chemoresistance
of cancer cells. We aimed to dissect the way MDSCs affect the cisplatin resistance phenotype of OC and
the related mechanisms.
Methods::
MDSCs were isolated from the spleen of OC mice isograft. CCK-8 and colony formation assays revealed
the effects of an MDSC-conditioned medium with dysregulated CD39 on the proliferation and cisplatin
sensitivity of OC cells. Fluorescence assay was used to reveal the effects of MDSCs with dysregulated CD39
on adenosine triphosphate (ATP) hydrolysis and adenosine (ADO) synthesis.
Results::
MDSCs with highly expressed CD39 could facilitate the proliferation and cisplatin resistance of OC
cells, while MDSCs with downregulated CD39 caused the opposite results. In addition, MDSCs with upregulated
CD39 could facilitate the hydrolysis of immunogenic ATP to immunosuppressive ADO, while the introduction
of CD39 inhibitor could repress such hydrolysis of ATP and generation of ADO, thereby abating the
proliferation and cisplatin resistance of OC cells.
Conclusion::
CD39+MDSC could promote the proliferation and cisplatin resistance of OC cells by generating
high concentrations of ADO, which indicates that targeting CD39+MDSC might be a feasible way to improve
cisplatin resistance in OC.
Funder
Zhejiang Medical Science and technology project
Natural Science Foundation of Zhejiang Province
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,Pharmacology