School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, Henan 450008, China.
Key Laboratory of Precision Oncology of Shandong Higher Education, Institute of Precision Medicine, Jining Medical University, Jining, Shandong 272067, China.
J Nat Prod. 2022 Aug 26;85(8):2006-2017. doi: 10.1021/acs.jnatprod.2c00400. Epub 2022 Aug 17.
Bladder cancer, specifically, muscle-invasive bladder cancer (MIBC), is among the most common malignant tumors. Patients with MIBC who cannot tolerate standard drugs require novel treatments. Targeting apoptosis may help treat cancer, which may be achieved with the use of some natural products. Nodosin, found in (Maxim.) Kudo (known as Xihuangcao), may inhibit bladder cancer cells. Transcriptomics and proteomics dual-omic analyses revealed the network pharmacological mechanism: (1) blocking the S phase by up-regulating RPA2, CLSPN, MDC1, PDCD2L, and E2F6 gene expressions, suppressing cancer cell proliferation; (2) inducing apoptosis and autophagy and restraining ferroptosis by up-regulating HMOX1, G0S2, SQSTM1, FTL, SLC7A11, and AIFM2 gene expressions; (3) preventing cancer cell migration by down-regulating NEXN, LIMA1, CFL2, PALLD, and ITGA3 gene expressions. , nodosin inhibited bladder cancer cell growth in a model of xenograft tumor in nude mice. This study is the first to report basic research findings on the network pharmacological mechanism of cytotoxicity of bladder cancer cells by nodosin, providing novel evidence for the application of nodosin in the field of oncology; however, other mechanisms may be involved in the effects of nodosin for further research. These findings provide a foundation for the development of novel MIBC drugs.
膀胱癌，特别是肌层浸润性膀胱癌（MIBC），是最常见的恶性肿瘤之一。对于不能耐受标准药物的 MIBC 患者，需要新的治疗方法。靶向细胞凋亡可能有助于治疗癌症，这可以通过使用一些天然产物来实现。从（Maxim.）Kudo（称为喜树）中发现的 nodosin 可能抑制膀胱癌细胞。转录组学和蛋白质组学双组学分析揭示了其网络药理学机制：（1）通过上调 RPA2、CLSPN、MDC1、PDCD2L 和 E2F6 基因表达，阻滞 S 期，抑制癌细胞增殖；（2）通过上调 HMOX1、G0S2、SQSTM1、FTL、SLC7A11 和 AIFM2 基因表达，诱导细胞凋亡和自噬并抑制铁死亡；（3）通过下调 NEXN、LIMA1、CFL2、PALLD 和 ITGA3 基因表达，抑制癌细胞迁移。在裸鼠异种移植肿瘤模型中，nodosin 抑制了膀胱癌细胞的生长。本研究首次报道了 nodosin 抑制膀胱癌细胞毒性的网络药理学机制的基础研究结果，为 nodosin 在肿瘤学领域的应用提供了新的证据；然而，nodosin 的作用可能还涉及其他机制，需要进一步研究。这些发现为开发新型 MIBC 药物提供了基础。
