Cannabinoid receptor 2 as a novel target for promotion of renal cell carcinoma prognosis and progression
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Renal cell carcinoma (RCC) is the most common malignancy of urogenital system, and patients with RCC may face a poor prognosis. However, limited curable therapeutic options are currently available. The aim of this study is to investigate the role of Cannabinoid receptor 2 (CB2) in RCC progression.
Immunohistochemistry was to investigate the expression pattern of CB2 in 418 RCC tissues and explore its prognostic function in RCC patients. Furthermore, the role of used CB2 si-RNA knockdown and inhibited by AM630, a CB2 inverse agonist, on cell proliferation, migration, and cell cycle of RCC cell lines in vitro was also investigated.
We observed that CB2 was up-regulated in RCC tissues, and presented as an independent prognostic factor for overall survival of RCC patients and higher CB2 expression tends to have poor clinical outcomes in survival analyses. Moreover, we also observed that CB2, incorporated with pN stage, pathological grade, and recurrence or distant metastasis after surgery, could obviously enhance their prognostic accuracy in a predictive nomogram analysis. In addition, knockdown or inhibition by AM630 for the expression of CB2 in vitro could significantly decreased cell proliferation and migration, and obviously induced cell cycle arrest in G2/M of RCC cells.
CB2 expression is functionally related to cellular proliferation, migration, and cell cycle of RCC cells. Our data suggest that CB2 might be a potential therapeutic target for RCC.
KeywordsRenal cell carcinoma Cannabinoid receptor 2 AM630
Renal cell carcinoma
Cannabinoid receptor 2
Clear-cell renal cell carcinoma
Fetal bovine serum
Harrell’s concordance index
Akaike information criteria
This work was supported by National Natural Science Foundation of China (nos. 81472378, 81272841, and 91129725), 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.
Jianfeng Wang, Yunze Xu, and Liangsong Zhu conceived and designed the experiments. Jianfeng Wang the manuscript and performed the experiments. Jianfeng Wang and Yunze Xu performed the immunohistochemistry assay. Jianfeng Wang and Liangsong Zhu performed the RNA interference (RNAi) transfection. Jianfeng Wang and Yun Zou performed the proliferative ability analysis. Jianfeng Wang, Wen Kong, Baijun Dong, and Jiwei Huang performed cell migration assay. Jianfeng Wang, Yonghui Chen and Wei Xue performed cell cycle analysis and statistical analysis. Yiran Huang and Jin Zhang oversight of all aspects of the study. All authors read and approved the final manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
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. Tissue samples were obtained with written consent from all the patients.
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