Overexpression of cannabinoid receptor 1 promotes renal cell carcinoma progression

Abstract

Renal cell carcinoma (RCC) is a common urologic tumor with a poor prognosis. Cannabinoid receptor 1 (CB1), which is a G protein-coupled receptor, has recently been reported to participate in the genesis and development of various cancers. However, the exact role of CB1 in RCC is unknown. The aim of this study was to determine the role of CB1 in RCC cell lines and RCC prognosis, thus underlying its potential as a therapeutic target. Immunohistochemistry and western blots were performed to investigate the expression of CB1 in RCC tissues and to determine its clinicopathological significance in RCC patients. Additionally, we explored CB1 expression in RCC cell lines and evaluated the effect of AM251, a CB1 inverse agonist, and in vitro siRNA knockdown of CB1 on the cellular proliferation, migration, and apoptosis of RCC cell lines. CB1 was overexpressed in cancerous tissues compared with adjacent normal tissues. Furthermore, CB1 expression levels were an independent risk factor for overall survival for RCC patients. AM251 significantly decreased tumor cell proliferation and induced cell apoptosis by upregulating the expression of the pro-apoptotic protein Bax and decreasing the expression of the anti-apoptotic proteins survivin and Bcl-2. Migration of the RCC cell lines was also significantly inhibited after treatment with AM251 compared with untreated control groups. In addition, knockdown of CB1 expression significantly decreased cell proliferation and invasion and significantly increased apoptosis of RCC cells. CB1 expression is functionally associated to cellular proliferation, apoptosis, and invasion ability of RCC. Our data suggest that CB1 might be a potential target for RCC clinical therapy.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 81472378, No. 81272841, and No. 91129725) and the Shanghai Committee of Science and Technology (13ZR1425100). All these study sponsors have no roles in the study design, in the collection, analysis, and interpretation of data.

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Correspondence to Wen Kong or Jin Zhang.

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This investigation was approved by the Ethics and Research Committees of Renji Hospital, Shanghai Jiao Tong University School of Medicine, and was conducted in accordance with the ethical standards and according to the Declaration of Helsinki and according to national and international guidelines.

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Jianfeng Wang and Yunze Xu contributed equally to this work

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Wang, J., Xu, Y., Zou, Y. et al. Overexpression of cannabinoid receptor 1 promotes renal cell carcinoma progression. Tumor Biol. 37, 16237–16247 (2016). https://doi.org/10.1007/s13277-016-5447-6

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Keywords

  • Renal cell carcinoma
  • Cannabinoid receptor 1
  • AM251