J Cancer 2020; 11(2):421-431. doi:10.7150/jca.31245

Research Paper

Blockade of Adenosine A2b Receptor Reduces Tumor Growth and Migration in Renal Cell Carcinoma

Ye Yi1*, Yihong Zhou2*, Xi Chu2, Xiaoping Zheng1, Deng Fei1, Jun Lei1, Huiyue Qi1, Yingbo Dai2✉

1. Department of Urology, The Third Xiangya Hospital of Central South University, No.138 Tongzipo Road, Changsha 410600, China.
2. Department of Urology, The fifth affiliated hospital Sun Yat-sen University, No.52 Meihua Dong Road, ZhuHai 519000, China.
* These authors contributed equally.

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Yi Y, Zhou Y, Chu X, Zheng X, Fei D, Lei J, Qi H, Dai Y. Blockade of Adenosine A2b Receptor Reduces Tumor Growth and Migration in Renal Cell Carcinoma. J Cancer 2020; 11(2):421-431. doi:10.7150/jca.31245. Available from https://www.jcancer.org/v11p0421.htm

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Adenosine A2b receptor (A2bR) is a member of the G protein-coupled receptor superfamily members, which has been considered involved in the pathogenesis of various cancers. However, little is known about the role of A2bR renal cell carcinoma (RCC). The A2bR expression levels in RCC 769-P and Caki-1 cell lines compared with HK-2 were analyzed by qRT-PCR. 769-P and Caki-1 cells were transfected with shRNA-A2bR to knock down the expression of A2bR. Cell proliferation was detected by MTT assays and colony formation assays. Wounding healing assays and transwell assays were used to evaluate the effects of A2bR on cell capacity of invasion and migration. Finally, potential mechanisms involved in A2bR blockade's effects on altered tumor behaviors were evaluated by western blotting. We showed that A2bR were significantly up-regulated in RCC cells compared to HK-2 cell. Functionally, MRS1754, a selective A2bR antagonist, and knocking-down the expression of A2bR by shRNA reduced proliferation and migration in vitro and tumor growth in vivo. Furthermore, we demonstrated that A2bR blockade inhibited tumor progression in part via the MAPK/JNK pathway. Conclusion: Our findings suggest the A2bR potentially plays an important role in RCC progression and A2bR blockade may be a promising candidate for therapeutic intervention for renal cell carcinoma.

Keywords: Adenosine A2b Receptor, MRS1754, MAPK/JNK signal pathway, Renal cell carcinoma.