Involvement of the arachidonic acid cytochrome P450 epoxygenase pathway in the proliferation and invasion of human multiple myeloma cells

PeerJ

article

Jing Shao¹  Hongxiang Wang²  Guolin Yuan³  Zhichao Chen¹  Qiubai Li¹ 

[1] Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology;Wuhan Central Hospital, Department of Hematology;Xiangyang Central Hospital, the Affiliated Hospital of Hubei University of Arts and Science, Department of Hematology

关键词: Multiple myeloma;    Proliferation;    Epoxyeicosatrienoic acids;    Cytochrome p450;    Apoptosis;    Migration;    Invasion;   

DOI  :  10.7717/peerj.1925

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

Cytochrome P450 (CYP) epoxygenases and the metabolites epoxyeicosatrienoic acids (EETs) exert multiple biological effects in various malignancies. We have previously found EETs to be secreted by multiple myeloma (MM) cells and to be involved in MM angiogenesis, but the role of the arachidonic acid cytochrome P450 epoxygenase pathway in the proliferation and mobility of MM cells remains unknown. In the present study, we found that MM cell lines generated detectable levels of 11,12-EET/14,15-EET and that increased levels of EETs were found in the serum of MM patients compared to healthy donors. The addition of exogenous EETs induced significantly enhanced proliferation of MM cells, whereas 17-octadecynoic acid (17-ODYA), an inhibitor of the CYP epoxygenase pathway, inhibited the viability and proliferation of MM cells. Moreover, this inhibitory effect could be successfully reversed by exogenous EETs. 17-ODYA also inhibited the motility of MM cells in a time-dependent manner, with a reduction of the gelatinolytic activity and protein expression of the matrix metalloproteinases (MMP)-2 and MMP-9. These results suggest the CYP epoxygenase pathway to be involved in the proliferation and invasion of MM cells, for which 17-ODYA could be a promising therapeutic drug.

【 授权许可】

CC BY