Expression And Significance Of Monocarboxylic Acid Transporter 4 In Esophageal Squamous Cell Carcinoma

Background Globally,esophageal cancer ranks ninth among common cancers and ranks sixth in cancer mortality.Most patients in China are esophageal squamous cell carcinoma.Common treatments are surgical treatment and radiotherapy and chemotherapy,but these treatment methods often do not reach the expected therapeutic effect of the patient.Therefore,a new treatment is needed to improve the survival rate of patients.The main role of Monocarboxylate transporter 4(MCT4)is to transport lactic acid produced by aerobic glycolysis during tumor cell energy metabolism to the outside of the cell.Many studies have confirmed that MCT4 is highly expressed in many tumors such as oral squamous cell carcinoma and colorectal cancer,and down-regulation of MCT4 expression can attenuate tumor cell proliferation,migration and invasion.This provides a new idea for the clinical treatment of malignant tumors.By searching MCT4 related literature,it was found that MCT4 was less studied in esophageal squamous cell carcinoma.This study will investigate the expression of MCT4 in esophageal squamous cell carcinoma(tissue,cell);the relationship between its expression level and clinical pathological parameters(lymphatic metastasis,clinical stage,etc.);and specifically down-regulate esophageal squamous cell carcinoma EC109 And MCT4 in EC9706 to explore the effects of MCT4 on its biologicalbehavior.Materials and Methods1.Materials1.1 The histopathological specimens of esophageal squamous cell carcinoma from November 1st,2014 to November 1st,2015 in our pathology department were selected,and the pathological specimens of adjacent tissues were taken.After screening according to the inclusion criteria and exclusion criteria,60 specimens of esophageal squamous cell carcinoma and 19 paracancerous tissues were selected.1.2 Normal esophageal epithelial cells Het1-A,esophageal squamous cell carcinoma EC109 and EC9706 were donated by our Institute of Digestion.2.Methods2.1 Immunohistochemistry was used to detect the expression of MCT4 in 60 cases of esophageal squamous cell carcinoma and 19 cases of adjacent tissues.The relationship between the expression level and clinical pathological parameters was analyzed.2.2 Western blot was used to detect the expression of MCT4 protein in esophageal epithelial cells Het1-A,esophageal squamous cell carcinoma cell line EC109 and EC9706.2.3 The transient transfection of siRNA was used to down-regulate the expression of MCT4 in esophageal squamous cell carcinoma EC109 and EC9706.The expression of MCT4 protein in each group was detected by Western blot.2.4 Using lactic acid assay kit,CCK8 kit,scratch and Transwell technology to detect the changes of intracellular and extracellular lactate levels,proliferation ability and migration and invasion ability of each group after down-regulating MCT4 expression.2.5 Statistical analysis was performed using SPSS16.0 statistical software.The expression of MCT4 in esophageal squamous cell carcinoma and its clinical pathological parameters were compared by chi-square analysis or Fisher’s exact test.Cell experiments and comparisons between groups were performed using one-way ANOVA with a test level of α = 0.05.Results 1.The results of immunohistochemistry showed that MCT4 had higher expressionrate in esophageal squamous cell carcinoma than in adjacent tissues(p<0.05),and it was related to tumor differentiation(P<0.05).However,it has nothing to do with factors such as clinical stage(P>0.05)and age(P>0.05).2.Western blot analysis showed that the expression of MCT4 in esophageal squamous cell carcinoma cells EC109 and EC9706 was higher than that of normal esophageal epithelial cells Het1-A(p<0.05).3.Western blot analysis showed that the expression of MCT4 protein in esophageal squamous cell carcinoma cells EC109 and EC9706 was decreased after transient transfection with siRNA(p<0.05).4.After down-regulating the expression of MCT4 in esophageal squamous cell carcinoma cells EC109 and EC9706,the lactic acid content of both cells increased(p<0.05),and the lactic acid content of both cells decreased(p<0.05).5.After down-regulation of MCT4 expression in EC109 and EC9706,the proliferation ability,migration ability and invasive ability of EC109 and EC9706 decreased(p < 0.05)..Conclusions1.MCT4 is highly expressed in esophageal squamous cell carcinoma,which is related to the degree of pathological differentiation.2.MCT4 was highly expressed in esophageal squamous cell carcinoma EC109 and EC9706,and down-regulation of MCT4 expression could weaken the ability of lactate transport,proliferation,migration and invasion of esophageal squamous cell carcinoma cells.