School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China; Inner Mongolia Key Laboratory of Molecular Biology, School of Basic Medical Sciences, Inner Mongolia Medical University, Hohhot, Inner Mongolia, 010058, China.
Inner Mongolia Key Laboratory of Molecular Biology, School of Basic Medical Sciences, Inner Mongolia Medical University, Hohhot, Inner Mongolia, 010058, China.
J Ethnopharmacol. 2022 Mar 1;285:114857. doi: 10.1016/j.jep.2021.114857. Epub 2021 Nov 20.
Renal cell carcinoma (RCC) is the most common cancer of the urinary system, the current treatments for RCC are unsatisfactory. Paeonol is the main pharmacologically active ingredient of the traditional Chinese medicine (TCM) moutan cortex (Paeonia suffruticosa Andrews) and Paeonia albiflora Pall, and has been used in TCM to treat various diseases including cancer. However, the underlying therapeutic mechanisms of paeonol in RCC have not been investigated yet.
This study aimed to explore the potential antitumor effects and mechanisms of paeonol on RCC based on network pharmacology and experimental validation.
Network pharmacological analysis was performed to predict the potential targets and mechanism of paeonol against RCC. The antitumor effects and the priority targets of paeonol against RCC were further assessed by in vitro experiments.
104 intersection targets shared by paeonol and RCC were collected, 15 hub genes were obtained, among these genes, VEGFA expression was higher in RCC, and the higher expression of IL-6 or lower expression of AKT1, JUN, MAPK1, and MAPK8 were correlated to the shorter overall survival (OS) in RCC patients. GO and KEGG analyses suggested that the genes were mainly enriched in the positive regulation of cell death and apoptosis pathway. In vitro experiments showed that paeonol inhibited 786-O cell proliferation, migration, invasion, and promoted apoptosis. When 786-O cells were treated with paeonol, the expression of Bax increased while Bcl-2 and VEGFA decreased.
The present study demonstrated that paeonol might play an essential role in RCC by regulating cell proliferation, apoptosis, metastasis, and invasion through the Bcl-2/Bax signaling pathway and VEGFA, providing a theoretical and experimental scientific basis for future investigations of the antitumor effects of paeonol against RCC.
肾细胞癌（RCC）是泌尿系统最常见的癌症，目前对 RCC 的治疗方法并不令人满意。丹皮酚是传统中药（TCM）牡丹皮（牡丹皮）和白芍（Paeonia albiflora Pall）的主要药理活性成分，已用于 TCM 治疗包括癌症在内的各种疾病。然而，丹皮酚治疗 RCC 的潜在治疗机制尚未得到研究。
本研究旨在基于网络药理学和实验验证探讨丹皮酚治疗 RCC 的潜在抗肿瘤作用和机制。
进行网络药理学分析以预测丹皮酚治疗 RCC 的潜在靶点和机制。通过体外实验进一步评估丹皮酚对 RCC 的抗肿瘤作用和优先靶点。
共收集丹皮酚与 RCC 的 104 个交集靶点，得到 15 个枢纽基因，其中 VEGFA 在 RCC 中表达较高，IL-6 表达较高或 AKT1、JUN、MAPK1、MAPK8 表达较低与 RCC 患者总生存期（OS）较短相关。GO 和 KEGG 分析表明，这些基因主要富集在细胞死亡和凋亡途径的正调控中。体外实验表明，丹皮酚抑制 786-O 细胞增殖、迁移、侵袭，并促进凋亡。当 786-O 细胞用丹皮酚处理时，Bax 表达增加，而 Bcl-2 和 VEGFA 表达减少。
本研究表明，丹皮酚可能通过调节 Bcl-2/Bax 信号通路和 VEGFA 来调节细胞增殖、凋亡、转移和侵袭，从而在 RCC 中发挥重要作用，为丹皮酚抗肿瘤作用的进一步研究提供了理论和实验科学依据。
