Ziyin Huatan Recipe, a Chinese herbal compound, inhibits migration and invasion of gastric cancer by upregulating RUNX3 expression
Ziyin Huatan Recipe, a Chinese herbal compound, inhibits migration and invasion of gastric cancer by upregulating RUNX3 expression
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滋阴化痰方通过上调RUNX3表达抑制胃癌迁移和侵袭
DOI：
10.1016/j.joim.2022.02.006
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Xiao-qiang Yue
中科院分区：
文献类型：
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作者：
Shang-jin Song;Xuan Liu;Qing Ji;Da-zhi Sun;Li-juan Xiu;Jing-yu Xu;Qi Li;Xiao-qiang Yue
目的：滋阴化痰方是由百合、半夏、白花蛇舌草等组成的传统中药，在治疗胃癌方面有良好的应用前景。然而，其潜在机制尚未得到明确解决。本研究旨在通过网络药理学分析，预测中药ZYHT治疗胃癌的作用靶点和分子机制，探讨ZYHT在体内外对胃癌的作用。方法：通过网络药理学分析预测ZYHT的作用靶点和分子机制。通过Western blot和实时定量聚合酶链反应进一步验证ZYHT对转移相关靶点表达的影响。为探讨ZYHT对细胞迁移和侵袭作用的分子机制，采用规则间隔短回文重复序列（clustered regularly interspaced short palindromic repeats/Cas9）敲除Runt-related transcription factor 3（RUNX 3）基因，并将慢病毒载体转染SGC-7901细胞。建立胃癌裸鼠肺转移模型，探讨滋阴活血汤的抗肿瘤转移作用。采用Western印迹和免疫组织化学方法探讨ZYHT对有或无RUNX 3基因的转移相关蛋白表达的影响。结果：网络药理学分析表明，ZYHT能抑制胃癌的粘着斑、迁移、侵袭和转移。ZYHT通过调节转移相关靶点的表达，抑制胃癌细胞的增殖、迁移和侵袭。敲除RUNX 3几乎完全逆转了ZYHT引起的细胞表型（迁移和侵袭）和蛋白表达水平。体内实验表明，ZYHT能抑制胃癌细胞的肺转移，延长裸鼠的生存时间。敲除RUNX 3可部分逆转胃癌细胞向肺的转移和ZYHT诱导的蛋白表达水平。结论：ZYHT在体内外均能有效抑制胃癌的侵袭和迁移，其分子机制可能与上调RUNX 3表达有关。
Objectives: Ziyin Huatan Recipe (ZYHT), a traditional Chinese medicine comprised of Lilii Bulbus, Pinelliae Rhizoma, and Hedyotis Diffusa, has shown promise in treating gastric cancer (GC). However, its potential mechanism has not yet been clearly addressed. This study aimed to predict targets and molecular mechanisms of ZYHT in treating GC by network pharmacology analysis and to explore the role of ZYHT in GC both in vitro and in vivo..Methods: Targets and molecular mechanisms of ZYHT were predicted via network pharmacology analysis. The effects of ZYHT on the expression of metastasis-associated targets were further validated by Western blot and quantitative real-time polymerase chain reaction. To explore the specific molecular mechanisms of the effects of ZYHT on migration and invasion, the runt-related transcription factor 3 (RUNX3) gene was knocked out by clustered regularly interspaced short palindromic repeats/Cas9, and lentiviral vectors were transfected into SGC-7901 cells. Then lung metastasis model of GC in nude mice was established to explore the anti-metastasis effect of ZYHT. Western blot and immunohistochemistry were used to explore the impact of ZYHT on the expression of metastasis-related proteins with or without RUNX3 gene..Results: The network pharmacology analysis showed that ZYHT might inhibit focal adhesion, migration, invasion and metastasis of GC. ZYHT inhibited the proliferation, migration and invasion of GC cells in vitro via regulating the expression of metastasis-associated targets. Knocking out RUNX3 almost completely reversed the cell phenotypes (migration and invasion) and protein expression levels elicited by ZYHT. In vivo studies showed that ZYHT inhibited the metastasis of GC cells to the lung and prolonged the survival time of the nude mice. Knocking out RUNX3 partly reversed the metastasis of GC cells to the lung and the protein expression levels elicited by ZYHT..Conclusion: ZYHT can effectively inhibit the invasion and migration of GC in vitro and in vivo, and its molecular mechanism may relate to the upregulation of RUNX3 expression.