Tanshinone I attenuates gastric precancerous lesions by inhibiting epithelial mesenchymal transition through the p38/STAT3 pathway

Abstract

BackgroundGastric 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. PurposeTo investigate the effect and mechanism of Tan-I in intervening GPLs, and provide a new therapeutic strategy for prevention of GC. MethodsGastric 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. ResultsTan-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. ConclusionThis 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.