“简云清华汤通过COL12A1介导的铁死亡信号通路抑制胃癌细胞的恶性行为。”
Jian Yun Qing Hua Decoction inhibits malignant behaviors of gastric carcinoma cells via COL12A1 mediated ferroptosis signal pathway.
发表日期:2023 Sep 12
作者:
Baoxinzi Liu, Yu Li, Yuanyuan Xu, Weiwei Xue, Zhichao Jin
来源:
Chinese Medicine
摘要:
《健桐青花汤》(JYQHD)是一种传统中药汤剂,已被应用于胃癌(GC)的治疗。我们试图证实JYQHD对胃癌的抗肿瘤效应,并探究JYQHD的作用机制。我们使用急性毒性试验来了解JYQHD的毒性。通过网络数据库研究COL12A1在GC组织中的表达和预后结果。利用几个基于网络的数据库,分析JYQHD的主要成分和靶点,以及胃癌已知的治疗靶点。利用文恩图获取重叠基因。利用潜在性病毒载体、shRNA和质粒转染GC细胞。通过细胞计数试剂盒-8(CCK8)法、球体形成法、丙二醛(MDA)、谷胱甘肽(GSH)、活性氧(ROS)、Fe2+、透射电子显微镜(TEM)、定量实时聚合酶链反应(qRT-PCR)、免疫印迹(WB)、免疫组织化学(IHC)等实验方法,研究COL12A1和JYQHD在GC中的作用和机制。结果显示,JYQHD无毒性且安全。JYQHD通过诱导GC细胞的铁死亡抑制了其生长和球体形成能力,并抑制了GC细胞引起的皮下异种移植瘤的生长。胃癌组织中COL12A1高表达,预示着不良预后。COL12A1通过抑制铁死亡特异性促进GC细胞的进展和干细胞特性。JYQHD下调COL12A1以通过诱导铁死亡抑制GC细胞的干细胞特性。COL12A1抑制了GC细胞的铁死亡,并增强了干细胞特性。JYQHD通过抑制COL12A1介导的铁死亡途径抑制了GC细胞的发展。© 2023. 中国医学与BioMed Central有限公司国际学会。
Jian Yun Qing Hua Decoction (JYQHD), a traditional Chinese medicine decoction, which has been applied in the treatment of gastric cancer (GC). We attempt to confirm the anti-gastric cancer effect of JYQHD and explore the mechanism of JYQHD.Acute toxicity test was used to understand the toxicity of JYQHD. We studied the expression and prognostic outcome of COL12A1 within GC tissues through the network databases. Using several web-based databases, we analyzed the major components and targets of JYQHD, as well as known therapeutic targets in gastric cancer. The Venn diagram was utilized to obtain the overlapped genes. Lentiviral vector, shRNAs and plasmids, were used to transfect GC cells. Cell counting kit-8 (CCK8), sphere formation, malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS), Fe2+, transmission electron microscopy (TEM), quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), Western-Blot (WB), and immunohistochemical (IHC) assays were employed to investigate the role and mechanism of COL12A1 and JYQHD in GC.The results showed that JYQHD was non-toxic and safe. JYQHD inhibited growth and sphere formation ability through inducing the ferroptosis of GC cells, and suppressed the GC cells induced subcutaneous xenograft tumor growth. COL12A1 was highly expressed in gastric cancer tissues, indicating poor prognosis. COL12A1 specifically enhanced GC cell progression and stemness via suppressing ferroptosis. JYQHD down-regulated COL12A1 in order to suppress the stemness of GC cells via inducing ferroptosis.COL12A1 inhibited ferroptosis and enhanced stemness in GC cells. JYQHD inhibited the development of GC cells by inhibiting cancer cell stemness via the ferroptosis pathway mediated by COL12A1.© 2023. International Society for Chinese Medicine and BioMed Central Ltd.