网络药理学研究和双组学分析揭示了天然产物 Nodosin 在体外和体内抑制肌肉浸润性膀胱癌的分子机制,Journal of Natural Products

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网络药理学研究和双组学分析揭示了天然产物 Nodosin 在体外和体内抑制肌肉浸润性膀胱癌的分子机制
Journal of Natural Products ( IF 3.3 ) Pub Date : 2022-08-17 , DOI: 10.1021/acs.jnatprod.2c00400
Xiaopeng Hao _{1,

2} , Huixia Fan ₂ , Jian Yang ₃ , Jinfu Tang ₃ , Junhui Zhou ₃ , Yuyang Zhao ₃ , Luqi Huang _{1,

3} , Yong Xia ₂

Affiliation

膀胱癌，特别是肌肉浸润性膀胱癌 (MIBC)，是最常见的恶性肿瘤之一。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。Nodosin，发现于Isodon serra（格言）工藤（称为西黄草），可抑制膀胱癌细胞。转录组学和蛋白质组学双组学分析揭示了网络药理机制：（1）通过上调RPA2、CLSPN、MDC1、PDCD2L、E2F6基因表达阻断S期，抑制癌细胞增殖；(2) 通过上调HMOX1、G0S2、SQSTM1、FTL、SLC7A11、AIFM2基因表达诱导细胞凋亡和自噬，抑制铁死亡；(3) 通过下调 NEXN、LIMA1、CFL2、PALLD 和 ITGA3 基因表达来阻止癌细胞迁移。体内, nodosin 在裸鼠异种移植肿瘤模型中抑制膀胱癌细胞生长。本研究首次报道了nodosin对膀胱癌细胞细胞毒作用的网络药理机制的基础研究成果，为nodosin在肿瘤领域的应用提供了新的证据；然而，其他机制可能与 nodosin 的作用有关，有待进一步研究。这些发现为开发新型 MIBC 药物提供了基础。

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Network Pharmacology Research and Dual-omic Analyses Reveal the Molecular Mechanism of Natural Product Nodosin Inhibiting Muscle-Invasive Bladder Cancer in Vitro and in Vivo

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 Isodon serra (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. In vivo, 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.

更新日期：2022-08-17

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