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阐明石蒜碱在肾细胞癌治疗中的抗癌潜力。

Elucidating the anticancer potential of dendrobine in renal cell carcinoma treatment.

作者信息

Jia Xing, Chen Zixuan, Chen Xingyu, Zhang Haojie, Sun Zongrun, Wang Zhou, Liu Min

机构信息

Department of Urology, Tongren Hospital Shanghai Jiao Tong University School of Medicine, No.1111 Xian Xia Road, Shanghai, 200336, China.

School of Health Policy and Management, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 Jan 7. doi: 10.1007/s00210-024-03774-5.

Abstract

Renal cell carcinoma (RCC) is the predominant form of kidney cancer. Despite the significant improvements in survival rates for advanced RCC patients due to targeted therapy and immunotherapy, challenges such as drug resistance and severe adverse reactions continue to hinder effective management. Therefore, there is an urgent need to identify new therapeutic agents for RCC. Natural products, derived from plants, animals, and microorganisms, are increasingly recognized for their potential in treating complex diseases such as cancer. Dendrobine, a natural product extracted from Dendrobium, holds significant anticancer potential. However, its role in anti-RCC therapy remains poorly understood. This study applied network pharmacology to explore the role of Dendrobine in RCC treatment, identifying STAT3 as a key target. Furthermore, a series of in vitro experiments confirmed that Dendrobine inhibits RCC cell growth. CCK-8 assays demonstrated that Dendrobine inhibits RCC cell viability in a concentration-dependent manner, with an IC50 of 142.5 μM for 786-O cells and 146.5 μM for A498 cells. Clonogenic formation assays and EdU staining confirmed that Dendrobine suppresses RCC cell proliferation. Wound healing and invasion assays showed that Dendrobine inhibits RCC cell migration and invasion. Hoechst 33342/PI co-staining demonstrated that Dendrobine induces apoptosis in RCC cells. Mechanistically, Western blot analysis revealed that Dendrobine targets the PI3K/Akt signaling pathway by inhibiting the expression of p-PI3K, p-Akt, and p-Erk. Overall, this study seeks to elucidate the underlying pharmacological mechanisms and provide new insights for potential therapeutic strategies in RCC.

摘要

肾细胞癌(RCC)是肾癌的主要形式。尽管由于靶向治疗和免疫治疗,晚期RCC患者的生存率有了显著提高,但耐药性和严重不良反应等挑战仍继续阻碍有效治疗。因此,迫切需要为RCC确定新的治疗药物。源自植物、动物和微生物的天然产物,因其在治疗癌症等复杂疾病方面的潜力而越来越受到认可。石斛碱是从石斛中提取的一种天然产物,具有显著的抗癌潜力。然而,其在抗RCC治疗中的作用仍知之甚少。本研究应用网络药理学探讨石斛碱在RCC治疗中的作用,确定信号转导和转录激活因子3(STAT3)为关键靶点。此外,一系列体外实验证实石斛碱可抑制RCC细胞生长。细胞计数试剂盒-8(CCK-8)检测表明,石斛碱以浓度依赖性方式抑制RCC细胞活力,对786-O细胞的半数抑制浓度(IC50)为142.5μM,对A498细胞的IC50为146.5μM。克隆形成实验和5-乙炔基-2'-脱氧尿苷(EdU)染色证实石斛碱可抑制RCC细胞增殖。伤口愈合和侵袭实验表明石斛碱可抑制RCC细胞迁移和侵袭。Hoechst 33342/碘化丙啶(PI)共染色表明石斛碱可诱导RCC细胞凋亡。机制上,蛋白质免疫印迹分析显示石斛碱通过抑制磷酸化磷脂酰肌醇-3激酶(p-PI3K)、磷酸化蛋白激酶B(p-Akt)和磷酸化细胞外信号调节激酶(p-Erk)的表达靶向磷脂酰肌醇-3激酶/蛋白激酶B(PI3K/Akt)信号通路。总体而言,本研究旨在阐明潜在的药理机制,并为RCC的潜在治疗策略提供新的见解。

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