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Adenosine Inhibits Ovarian Cancer Growth Through Regulating RhoGDI2 Protein Expression

Authors Xia B, Wang J

Received 11 June 2019

Accepted for publication 18 October 2019

Published 8 November 2019 Volume 2019:13 Pages 3837—3844

DOI https://doi.org/10.2147/DDDT.S219028

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Dragan Hrncic

Peer reviewer comments 2

Editor who approved publication: Dr Anastasios Lymperopoulos


Bing Xia, Jing Wang

Hunan Cancer Hospital and the Affiliated Tumor Hospital of Xiang-Ya School of Medicine, Central South University, Changsha 410078, People’s Republic of China

Correspondence: Jing Wang
Hunan Cancer Hospital and the Affiliated Tumor Hospital of Xiang-Ya School of Medicine, Central South University, 283 Tongzipo Road, Yuelu District, Changsha 410078, People’s Republic of China
Tel +86 135 4865 1043
Email wangjing_hnzyyy@163.com

Objective: This study aimed to investigate the effect of adenosine (Ado) on the growth of ovarian cancer and to explore the related mechanisms.
Methods: The effect of Ado on the proliferation of A2780 human ovarian cancer cells was examined according to the MTT method. Moreover, the nude mouse model of subcutaneous A2780 xenograft was constructed, and then, Ado and cisplatin were administered intraperitoneally to investigate the effect of Ado on tumor growth in vivo. Immunohistochemistry (IHC) was carried out to study the effect of Ado on the expression of Rho-specific guanine nucleotide dissociation inhibitor 2 (RhoGDI2) in the subcutaneous xenografts. Afterwards, the commercially constructed RhoGDI2 siRNA plasmid was transfected into A2780 cells, and tube formation assay was conducted to determine the effect of down-regulating RhoGDI2 expression on the regulation of angiogenesis in ovarian cancer by Ado. Besides, Western blotting was performed to detect the effect of RhoGDI2 down-regulation on the regulation of matrix metalloproteinase 2 (MMP-2), MMP-9, vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-β), tumor necrosis factor (TNF-α), and platelet endothelial cell adhesion molecule-1 (PECAM-1 or CD31) expression in ovarian cancer cells by Ado.
Results: The relative viability of cells subsequent to Ado treatment proved to be both concentration- and time dependent. IHC results showed that Ado evidently enhanced the RhoGDI2 protein expression. In addition, interference with RhoGDI2 outstandingly attenuated the ability of Ado to suppress tumor cell invasion and induce angiogenesis in vitro. Furthermore, molecular mechanism studies indicated that Ado remarkably inhibited the expression of MMP-2, MMP-9, VEGF, TGF-β, TNF-α, and CD31, while interference with RhoGDI2 restored the expression of the above-mentioned angiogenic factors.
Conclusion: Ado inhibits the growth of A2780 human ovarian cancer cells through inhibiting tumor cell invasion and angiogenesis in a RhoGDI2-dependent manner.

Keywords: adenosine, ovarian cancer, RhoGDI2, invasion, growth, angiogenesis

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