Wang Jianfeng, Xu Yunze, Zhu Liangsong, Zou Yun, Kong Wen, Dong Baijun, Huang Jiwei, Chen Yonghui, Xue Wei, Huang Yiran, Zhang Jin
Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
J Cancer Res Clin Oncol. 2018 Jan;144(1):39-52. doi: 10.1007/s00432-017-2527-y. Epub 2017 Oct 9.
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.
肾细胞癌(RCC)是泌尿生殖系统最常见的恶性肿瘤,RCC患者预后可能较差。然而,目前可治愈的治疗选择有限。本研究旨在探讨大麻素受体2(CB2)在RCC进展中的作用。
采用免疫组织化学方法研究418例RCC组织中CB2的表达模式,并探讨其在RCC患者中的预后功能。此外,还研究了使用CB2 si-RNA敲低和CB2反向激动剂AM630抑制对RCC细胞系体外细胞增殖、迁移和细胞周期的作用。
我们观察到CB2在RCC组织中上调,并在生存分析中作为RCC患者总生存的独立预后因素,CB2表达越高,临床结局往往越差。此外,在预测列线图分析中,我们还观察到CB2与pN分期、病理分级以及术后复发或远处转移相结合,可明显提高其预后准确性。此外,体外敲低或用AM630抑制CB2表达可显著降低RCC细胞的增殖和迁移,并明显诱导细胞周期阻滞在G2/M期。
CB2表达与RCC细胞的细胞增殖、迁移和细胞周期功能相关。我们的数据表明CB2可能是RCC的一个潜在治疗靶点。