Department of Urology, Shanghai General Hospital of Nanjing Medical University, Shanghai 200080, P.R. China.
Department of Urological Surgery, Ningbo Urology and Nephrology Hospital, Ningbo, Zhejiang 315000, P.R. China.
Mol Med Rep. 2018 May;17(5):7403-7408. doi: 10.3892/mmr.2018.8732. Epub 2018 Mar 14.
Renal cell carcinoma (RCC), which is derived from the proximal tubules of nephrons, is one of the most common solid cancers. Due to its inherent insensitivity to radiotherapy and chemotherapy, surgery remains the only curative strategy for RCC. Therefore, a novel strategy for treating RCC is urgently needed. This study aims to investigate the effects of dauricine, a bisbenzylisoquinoline alkaloid, in RCC cells and the underlying mechanisms of its action. The effects of dauricine on viability, cell cycle distribution and apoptosis in RCC cells were determined in vitro by MTT assay, flow cytometry and nucleosome ELISA assay, respectively. Mechanism studies were performed by analyzing related proteins using western blotting assays. We show that dauricine effectively inhibits the viability of four RCC cell lines (786‑O, Caki‑1, A‑498 and ACHN). In addition, dauricine induces cell cycle arrest at the G0/G1 phase in RCC cells. Dauricine also induces apoptosis via the intrinsic pathway, since caspase‑9 and caspase‑3 but not caspase‑8 activation was detected after the treatment. Moreover, dauricine was able to inhibit the PI3K/Akt signaling pathway. Our findings suggest inhibitory effects of dauricine in renal cancer cells and provide a better understanding of its underlying mechanism. Our findings suggest that dauricine could be a potential therapeutic agent for treating RCC.
肾细胞癌（RCC）来源于肾单位的近端小管，是最常见的实体瘤之一。由于其对放疗和化疗固有不敏感，手术仍然是 RCC 的唯一治愈策略。因此，迫切需要一种治疗 RCC 的新策略。本研究旨在探讨蝙蝠葛碱（一种双苄基异喹啉生物碱）在 RCC 细胞中的作用及其作用机制。通过 MTT 测定法、流式细胞术和核小体 ELISA 测定法分别测定了蝙蝠葛碱对 RCC 细胞活力、细胞周期分布和细胞凋亡的影响。通过 Western blot 分析相关蛋白来进行机制研究。我们表明蝙蝠葛碱可有效抑制四种 RCC 细胞系（786-O、Caki-1、A-498 和 ACHN）的活力。此外，蝙蝠葛碱诱导 RCC 细胞中的细胞周期停滞在 G0/G1 期。蝙蝠葛碱还通过内在途径诱导细胞凋亡，因为在用蝙蝠葛碱处理后检测到 caspase-9 和 caspase-3 的激活，但未检测到 caspase-8 的激活。此外，蝙蝠葛碱能够抑制 PI3K/Akt 信号通路。我们的研究结果表明蝙蝠葛碱对肾癌细胞具有抑制作用，并提供了对其潜在机制的更好理解。我们的研究结果表明，蝙蝠葛碱可能是治疗 RCC 的潜在治疗剂。
