| Background and purposeGlobally,gastric cancer remains one of important cancers.It is incidence and mortaliy rate rank the third among all cancers in our country.Although there are a variety of treatment modes including radiotherapy,chemotherapy,immunotherapy,endoscopy and surgical resection,the five-year survival rate of patients with gastric cancer is still not satisfactory.Exploring the molecular mechanism of tumor invasion and metastasis is critical for patients with advanced gastric cancer to determine clinically effective chemotherapeutic drugs.Because of the unique advantages of remarkable anti-cancer effect,small side effects and numerous targets,the monomer of traditional Chinese medicine has become the focus of researchers at home and abroad.Liensinine is one of the effective components of the traditional Chinese medicine lotus seed heart.A large number of research data suggest that it has great medicinal potential in tumor treatment.The present study was designed to evaluate the effect of liensinine on epithelial-mesenchymal transformation of gastric cancer cells(HGC-27 and MGC-803),to explore its underlying relevant molecular mechanism,and to promote the clinical transformation of natural compounds.MethodsGastric cancer cells(HGC-27 and MGC-803)were intervened with liensinine at a specified concentration(determined by the experimental purpose).MTT and colony formation experiments were performed to detect the survival rate and proliferation of gastric cancer cells at different times points and concentrations after liensinine treatment.Wound healing and Transwell assays were used to measure the changes of migration and invasion ability of gastric cancer cells before and after the intervention of liensinine.The protein expression levels of E-cadherin,Vimentin,N-cadherin,MMP-2/-9,Snail,Slug,Akt,p-Akt,ERK1/2 and p-ERK1/2 in gastric cancer cells treated with different concentrations of liensinine were detected by Western blot.The expression levels of E-cadherin and Vimentin in gastric cancer cells treated with different concentrations of liensinine were qualitatively evaluated by Immunofluorescence.ResultsMTT results suggestd that the activity of gastric cancer cells(HGC-27 and MGC-803)decreased gradually with the increase of liensinine concentration.The colony formation experiment indicated that liensinine could significantly decrease the ability of long-term proliferation of gastric cancer cells.Wound healing and Transwell experiments demonstrated that the motility of gastric cancer cells was weaken by liensinine.Western blot results found that with the increase of liensinine concentration,the expression of E-cadherin gradually upregulated,while the expression of Vimentin,N-cadherin,Snail,Slug,MMP-9 and MMP-2 downregulated.With elevated liensinine concentration,the expression levels of AKT and ERK1/2 in gastric cancer cells almost did not change,while the expression levels of p-AKT and p-ERK1/2 significantly reduced.Immunofluorescence staining displayed that E-cadherin fluorescence intensity increased after liensinine intervention in gastric cancer cells,while Vimentin fluorescence intensity decreased.ConclusionsThis study demonstrated that LIE can inhibit the invasion and metastasis of GC cells by regulating tumor EMT.Additionally,liensinine may reduce the expression of vimentin and N-cadherin and increase the expression of E-cadherin by blocking the PI3K/AKT and ERK/MAPK signal transduction pathways.This mechanism indicates liensinine can be used as a natural small molecular chemotherapeutic drug to offer a novel and valuable strategy for the treatment of advanced gastric cancer,and is expected to become an excellent inhibitor of AKT and ERK1/2. |
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