The Study On The Function And Mechanism Of Cystine/glutamate Antiporter SLC7A11 In Gastric Cancer

Objective:Gastric cancer is one of the most common malignant tumors in the world.The rates of morbidity and mortality are a little higher in the world.However,China is a country with a high incidence of gastric cancer worldwide,and the number of cases of morbidity and mortality is relatively large,which seriously affects the health of patients.And then,the disease burden of the patients is too heavy,which is the focus of tumor prevention and treatment.Solute carrier family 7,membrane 11(SLC7A11),is a key component of the amino acid transporter system Xc~-together with its binding partner SLC3A2.The primary function of system Xc~-is to uptake cystine in exchange for glutamate.Cystine is essential for glutathione synthesis,a major cofactor of the endogenous antioxidant program.Recent studies have found that SLC7A11 is distributed in a variety of cancer tissues,such as breast cancer,malignant melanoma,liver cancer,etc.,and is highly expressed in these malignant tumors,which is closely related to the pathogenesis of cancer.However,the role of SLC7A11 in the development of gastric cancer is not yet clear.About this study,the aim was to explore the expression level of the SLC7A11and the mechanism of its action in gastric cancer.Methods:Detecting the expression of the SLC7A11 in gastric cancer tissue level,30 cases of gastric cancer tissue collected from the hospital,and the corresponding tissue adjacent to carcinoma,using experimental method of the immunohistochemical staining and the Real-Time PCR detection the SLC7A11 expression level,analysis whether it makes sense between the pathological indicators of gastric cancer and the SLC7A11expression level;Survival analysis of gastric cancer was performed using the Kaplan Meier database.In addition,the SLC7A11 expression was detected at the level of gastric cancer cells,and Sorafenib and Erastin,the SLC7A11 inhibitor,were used to treat cells to observe the ability of inhibiting the growth and the clonal formation of gastric cancer cells in vitro.We treated the cell lines BGC-823 with si SLC7A11,knocking down the expression of the SLC7A11.And then,the effect of Real-Time PCR on the expression level of h TERT was detected.Results:The Immunohistochemical method was used to explore that the expression level of the SLC7A11 in gastric cancer tissue was distinctly higher than that in corresponding adjacent gastric mucosa as the control;The experimental method of Real-Time PCR was used to find that the expression level of the SLC7A11 in cancer tissues was also obviously higher than that in the corresponding adjacent gastric mucosa as the control,and the expression level of h TERT in gastric cancer was also obviously higher than that in the corresponding adjacent gastric mucosa.Both protein level and gene level suggested that SLC7A11 was highly expressed in gastric cancer tissues.The Kaplan-Meier database was used to find that the median survival time of patients with gastric cancer in the high expression group of SLC7A11 was distinctly lower than that in the low expression group.The analysis of the SLC7A11 gene expression and clinical pathological factors showed that the expression of the SLC7A11 gene was obviously correlated with TNM staging of gastric cancer.In addition,at the cellular level,gastric cancer cells were treated with si SLC7A11.Real-Time PCR results showed that the expression level of h TERT in gastric cancer cell lines with the si SLC7A11 was also significantly reduced.CCK-8 test showed that the growth of gastric cancer cells treated with Sorafenib and Erastin was inhibited after 48h.The clone formation experiment results showed that the number of gastric cancer cells treated by Sorafenib and Erastin was significantly lower than that of the control group.Conclusion:The SLC7A11 is highly expressed in gastric cancer tissues.At the m RNA level of the expression level of the SLC7A11 in cancer tissues was distinctly higher than that in the corresponding adjacent gastric mucosa.And the same trend was observed in the h TERT,suggesting that SLC7A11 may be a new marker for the diagnosis of gastric cancer,and the SLC7A11 may be associated with the h TERT in the development of gastric cancer.However,at the cellular level,knocking down or inhibiting the SLC7A11 gene expression,the expression level of the h TERT was also reduced,the ability of the growth and cloning of gastric cancer cells was inhibited.The SLC7A11 gene can promote tumor growth.The SLC7A11 is likely to participate in gastric cancer formation mechanism;Exploring the specific mechanism of action between the SLC7A11 and the h TERT may provide new ideas and methods for the future to treat cancer.