Liang Dan, Tang Shiyun, Liu Lu, Zhao Maoyuan, Ma Xiao, Zhao Yanling, Shen Caifei, Liu Qingsong, Tang Jianyuan, Zeng Jinhao, Chen Nianzhi
Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Int Immunopharmacol. 2023 Nov;124(Pt A):110902. doi: 10.1016/j.intimp.2023.110902. Epub 2023 Sep 10.
Gastric precancerous lesions (GPLs) are omens for gastric cancer (GC), which developing with a series of pathological changes of gastric mucosa. Reversing epithelial-mesenchymal transition (EMT) in gastric mucosa is the main approach to restrain GPLs from evolving into cancer. Tanshinone I (Tan-I), the active ingredients of traditional Chinese herb Salvia miltiorrhiza, has exhibited anticancer effect.
To investigate the effect and mechanism of Tan-I in intervening GPLs, and provide a new therapeutic strategy for prevention of GC.
Gastric mucosal epithelial cells were treated with the N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) to construct MNNG-induced cell (MC cell) of gastric mucosa that undergoing EMT process. Then, this study explored the effect and mechanism of Tan-I in vitro. Subsequently, this study constructed GPL mice to clarify the exact efficacy and mechanism of Tan-I on GPLs.
Tan-I inhibited MC cell proliferation, invasion and migration. Simultaneously, the aberrant expression of E-cadherin and N-cadherin were reversed. Tan-I attenuated inflammation by reducing the release of nitric oxide, TNFα and IL-1β. Tan-I reversed the EMT and inflammatory processes by regulating p38 and STAT3.
This study showed that Tan-I inhibited the progression of GPLs by reversing the EMT process and reducing inflammation by restraining the p38/STAT3 signaling pathway.
胃癌前病变（GPLs）是胃癌（GC）的预兆，其随着胃黏膜的一系列病理变化而发展。逆转胃黏膜上皮-间质转化（EMT）是抑制GPLs演变为癌症的主要途径。丹参酮I（Tan-I）是传统中药丹参的活性成分，已显示出抗癌作用。
研究Tan-I干预GPLs的作用及机制，为GC的预防提供新的治疗策略。
用N-甲基-N'-硝基-N-亚硝基胍（MNNG）处理胃黏膜上皮细胞，构建经历EMT过程的MNNG诱导的胃黏膜细胞（MC细胞）。然后，本研究在体外探索Tan-I的作用及机制。随后，本研究构建GPL小鼠以阐明Tan-I对GPLs的确切疗效和机制。
Tan-I抑制MC细胞增殖、侵袭和迁移。同时，E-钙黏蛋白和N-钙黏蛋白的异常表达得到逆转。Tan-I通过减少一氧化氮、TNFα和IL-1β的释放减轻炎症。Tan-I通过调节p38和STAT3逆转EMT和炎症过程。
本研究表明，Tan-I通过逆转EMT过程并通过抑制p38/STAT3信号通路减轻炎症来抑制GPLs的进展。
