Baicalein Inhibits The Invasion And Migration Of Gastric Cancer BGC-823 Cells And Epithelial-mesenchymal Transition Through NF-κB/snail Signaling Pathway

Gastric cancer is one of the most common malignant tumors.In China,the incidence rate of gastric cancer is second,and the mortality rate is third.The etiology of gastric cancer remains unclear.The occurrence and development of gastric cancer is a complex pathological process involving multiple factors,multiple steps and multiple genes.Tumor invasion and metastasis is the leading cause of death in patients with gastric cancer.Many scholars are committed to the study of the occurrence,development,invasion and metastasis mechanisms in gastric cancer,and effort to explore effective treatment of gastric cancer.Epithelial mesenchymal transition(EMT)is the biological process of epithelial cells transforming into mesenchymal cells.Its main feature is that epithelial cells lose epithelial properties and obtain interstitial cell characteristics.EMT is an important evolution of tumor cells and is one of the key steps in the invasion and metastasis of epithelial-derived malignant tumors.Cancer cells in the event of EMT,accompanied by increased invasion and migration capacity,and thus promote the tumor metastasis.Traditional Chinese medicine is a safe and effective method for the treatment of cancer,which has attracted worldwide attention in the field of cancer treatment.There are more and more researches on the treatment of malignant tumors with traditional Chinese medicine.The composition of traditional Chinese medicine is complex,the mechanism of action is unique,and it is usually "multi ways,multi targets" to play an anti-tumor effect.Traditional Chinese medicine has great potential and irreplaceable advantages in the treatment of cancer.Baicalein is an effective component extracted from the dried root of Scutellaria baicalensis georgi and belong to flavonoids monomer compounds.Baicalein has multiple pharmacological effects.In recent years,it has been found that baicalein can inhibit many kinds of cancer,showing a strong broad-spectrum antitumor activity.The mechanism can be summarized as follows:to induce tumor cell apoptosis,to block cell cycle,inhibition of new tumor angiogenesis,inhibition of invasion and metastasis and regulation of related signaling pathways of invasion and metastasis.Objective:Our study aimed to investigate the effects of Baicalein on the invasion and migration of gastric cancer BGC-823 cells and epithelial-mesenchymal transition(EMT).To verify the effect of Baicalein further in vivo,we use patient-derived tumor tissue(PDTT)xenograft models.Method:Study in vitro:Different concentrations of baicalein were used to treat BGC-823 cells,MTT colorimetry was used to observe the inhibitory rate of cell proliferation.The effects of baicalein on theinvasion and migration ability of gastric cancer BGC-823 cells were determined by cell invasion and migration assay.Study in mechanism:The roles of baicalein on EMT of BGC-823 cells were investigated by detecting the protein levels of EMT related markers in BGC-823 cells after baicalein and/or TGF-β1 treatment by western blot,finally,the role of baicalein in TGF-β1-mediated activation of NF-KB/Snail signaling pathway were investigated by detecting the protein levels of the factors involved in NF-κB/Snail signaling pathway in BGC-823 cells after baicalein and/or TGF-β1 treatment by western blot.Study in vivo:GC patient derived tumor models were established to test the antitumor efficacy of Baicalein.During the treatment,we measured the volume of xenografts periodically to verify the effect of Baicalein on these tumors;weigh the weight of xenografts to learn the adverse reaction.After the treatment,immunohistochemistry(IHC)was applied to analyze the effect of Baicalein.Results:Effects in vitro:Our data have shown that baicalein not only can inhibit the proliferation of BGC-823 cells but also can reduce the invasion and migration ability of those cells.Baicalein can inhibit EMT of BGC-823 and TGF-β1-mediated activation of NF-κB/Snail signaling pathway by regulating the expression of the related factors.Effects in vivo:In PDTT models,Baicalein suppressed tumor growth.The results of immunohistochemistry in the baicalein group can further support the results of baicalein in vitro.Conclusion:These data showed that baicalein could inhibit EMT and suppress the invasion and migration of human gastric cancer BGC-823 through NF-κB/Snail signaling pathway.Baicalein can play a role with anti-tumor effect in vitro and in vivo experiments,Baicalein may be a potential drug for the treatment of gastric cancer.