The Impact and Mechanisms of Glutamine Transporter SLC1A5 on the Malignant Biology of Esophageal Cancer Cells

ZHAO Huashan; ZHANG Xudong; CHEN Lele; JIN Xing; ZHOU Kexu; DU Yue; GAO Shegan; ZHANG Xiusen

doi:10.15926/j.cnki.issn2096-7381.2024.01.002

Abstract：Objective To investigate the expression of glutamine transporter SLC1A5 in esophageal squamous cell carcinoma cell lines and its impact on proliferation and invasion,as well as its underlying mechanisms.Methods Real-time quantitative PCR and immuno-blotting were employed to measure the expression levels of SLC1A5 in human normal esophageal epi-thelial cell line(SHEE)and esophageal squamous cell carcinoma cell lines(KYSE30,KYSE70,KYSE140,TE1).The CRISPR/Cas9 system was used to knock out SLC1A5 in KYSE70 cells,which exhibited high expression level of SLC1A5.The pro-liferation and migration ability of esophageal cancer KYSE70 cells were measured using CCK8 assay and scratch assay between control,knockout of SLC1A5,and use of SLC1A5 inhibitor V-9302 groups.Gluta-mine metabolism in KYSE70 cells was examined by GSH/GSSG assay following the same conditions.Results SLC1A5 was found to be highly expressed in the esophageal squamous cell carcinoma cell line KYSE70,showing significant differences compared to its expres-sion in normal esophageal epithelial cells(P<0.05).Upon knockout of SLC1A5 and treatment with the SLC1A5 inhibitor V-9302,the proliferation capacity of KYSE70 tumor cells was significantly reduced com-pared to the untreated cell group(P<0.05).The migration area of the scratch assay was significantly de-creased in the treated groups compared to the untreated group(P<0.05).The GSH/GSSG ratio assay dem-onstrated that the knockout of SLC1A5 and treatment with the SLC1A5 inhibitor V-9302 led to a significant decrease in the GSH/GSSG ratio compared to the untreated group(P<0.05).Conclusion SLC1A5 is highly expressed in esophageal squamous cell carcinoma cell lines.Inhibiting SLC1A5 can effectively reduce the proliferation and migration abilities of esophageal cancer cells,as well as decrease glutamine metabolism.These findings provide new insights for the treatment of esophageal cancer.