Wang Sitong, Wu Chenxi, Li Yinghong, Ye Bin, Wang Shuai, Li Guowang, Wu Jiawei, Liu Shengnan, Zhang Menglong, Jia Yongsen, Cao Huijuan, Jiang Chunhua, Wu Fanwu
Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine for Diabetes and Its Complications, College of Traditional Chinese Medicine, North China University of Science and Technology, Tangshan, China.
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
Front Pharmacol. 2022 Jul 12;13:922457. doi: 10.3389/fphar.2022.922457. eCollection 2022.
Tumours are among the most lethal diseases that heavily endanger human health globally. Xuefu Zhuyu Decoction (XFZYD) is a prescription used to treat blood-activating stasis. Although XFZYD has been shown to suppress migration and invasion of tumour cells, the active ingredients, potential targets, and underlying mechanism remain largely elusive. To identify the prospective ingredients and major targets of XFZYD against tumours, and evaluate the efficacy and potential molecular mechanisms of XFZYD extract on tumour growth and invasion. We predicted that XFZYD might act on 80 targets through 128 active components using the network pharmacology analysis method. In addition, we prepared an XFZYD aqueous extract and employed the Ras/ -induced tumour model to carry out experimental verification. XFZYD did not exhibit any side effects on development, viability, and fertility. Furthermore, XFZYD significantly impeded tumour size and invasion at moderate concentrations and suppressed the increased phosphorylation of JNK but strongly enhanced the expression of Caspase 3 in the Ras/ model. Finally, the mRNA level of the transcription complex AP-1 component was remarkably reduced. In contrast, the transcription of three pro-apoptotic genes was significantly increased when XFZYD was used to treat the tumour model. The study findings suggest that XFZYD may promote tumour cell apoptosis by activating caspase signalling to control primary growth and hinder tumour cell invasion by suppressing JNK/AP-1 signalling activity, thus providing a potential therapeutic strategy for XFZYD in the clinical treatment of cancer and other related diseases.
肿瘤是全球严重危害人类健康的最致命疾病之一。血府逐瘀汤（XFZYD）是一种用于活血化瘀的方剂。虽然已证明血府逐瘀汤可抑制肿瘤细胞的迁移和侵袭，但其活性成分、潜在靶点和潜在机制仍 largely 难以捉摸。为了确定血府逐瘀汤抗肿瘤的潜在成分和主要靶点，并评估血府逐瘀汤提取物对肿瘤生长和侵袭的疗效及潜在分子机制。我们使用网络药理学分析方法预测血府逐瘀汤可能通过 128 种活性成分作用于 80 个靶点。此外，我们制备了血府逐瘀汤水提取物，并采用 Ras/ -诱导的肿瘤模型进行实验验证。血府逐瘀汤对发育、生存能力和生育能力未表现出任何副作用。此外，在中等浓度下，血府逐瘀汤显著阻碍肿瘤大小和侵袭，并抑制 Ras/ 模型中 JNK 磷酸化的增加，但强烈增强 Caspase 3 的表达。最后，转录复合物 AP-1 成分的 mRNA 水平显著降低。相反，当用血府逐瘀汤治疗肿瘤模型时，三个促凋亡基因的转录显著增加。研究结果表明，血府逐瘀汤可能通过激活 caspase 信号通路促进肿瘤细胞凋亡以控制原发性生长，并通过抑制 JNK/AP-1 信号活性阻碍肿瘤细胞侵袭，从而为血府逐瘀汤在癌症及其他相关疾病的临床治疗中提供了一种潜在的治疗策略。
