Fang Zhiqing, Tang Yueqing, Jiao Wei, Xing Zhaoquan, Guo Zhaoxin, Wang Weichang, Xu Zhonghua, Liu Zhaoxu
Department of Urology, Qilu Hospital of Shandong University, Ji'nan, Shandong, China; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Ji'nan, Shandong, China.
Department of Urology, Qilu Hospital of Shandong University, Ji'nan, Shandong, China.
Food Chem Toxicol. 2014 Apr;66:210-6. doi: 10.1016/j.fct.2014.01.049. Epub 2014 Feb 5.
Nitidine chloride (NC), a natural bioactive alkaloid derived from Zanthoxylum nitidum (Roxb) DC, has been shown to have inhibitory effects on various tumors. However, whether NC could exert anti-cancer activity and the underlying mechanisms have not been elucidated in renal cancer cells. In this study, we demonstrated the growth inhibitory and pro-apoptotic effects of NC on renal cancer cells both in vitro and in vivo. With cell viability and flow cytometric apoptosis assays, we found that NC potently suppressed the growth of 786-O and A498 cells in a time- and dose- dependent manner. Consistently, the xenograft model performed in nude mice exhibited reduced tumor growth with NC treatment. Mechanically, we presented that NC significantly decreased phosphorylation of ERK and Akt, accompanied by up-regulation of P53, Bax, cleavage caspase-3 and cleavage PARP, downregulation of Bcl-2, caspase-3 and PARP. Furthermore, a specific MEK inhibitor, PD98059, could potentiate the pro-apoptotic effects of NC, which indicated that NC might trigger apoptosis in renal cancer cells partly via inhibition of ERK activity. Taken together, our results imply that NC could be developed as a potential anticancer agent to renal cancer and worthy of further studies.
氯化两面针碱（NC）是一种从两面针中提取的天然生物活性生物碱，已被证明对多种肿瘤具有抑制作用。然而，NC是否能在肾癌细胞中发挥抗癌活性及其潜在机制尚未阐明。在本研究中，我们证明了NC在体外和体内对肾癌细胞均具有生长抑制和促凋亡作用。通过细胞活力和流式细胞术凋亡检测，我们发现NC能以时间和剂量依赖性方式有效抑制786-O和A498细胞的生长。同样，在裸鼠中进行的异种移植模型显示，NC治疗可使肿瘤生长减缓。机制上，我们发现NC显著降低ERK和Akt的磷酸化水平，同时上调P53、Bax、裂解的caspase-3和裂解的PARP，下调Bcl-2、caspase-3和PARP。此外，一种特异性MEK抑制剂PD98059可增强NC的促凋亡作用，这表明NC可能部分通过抑制ERK活性触发肾癌细胞凋亡。综上所述，我们的结果表明NC有望开发成为一种潜在的肾癌抗癌药物，值得进一步研究。
