SLC7A11在食管鳞癌组织中的表达及其介导肿瘤细胞代谢的初步探究OA
Expression of SLC7A11 in esophageal squamous cell carcinoma tissues and its preliminary study on mediating tumor cell metabolism
目的 探讨溶质载体家族7成员11蛋白(SLC7A11)在食管鳞癌(ESCC)中的表达及其与临床预后之间的关系以及如何影响ESCC细胞增殖、迁移等生物学过程.方法 利用免疫组化技术分析310例ESCC和259例癌旁正常对照组织样本的SLC7A11蛋白表达.分析SLC7A11蛋白与ESCC患者的临床病理特征和预后之间的关系.使用siRNA抑制ESCC细胞系中SLC7A11基因的表达,利用CCK-8、平板克隆形成、Transwell实验探究敲低SLC7A11基因表达对ESCC细胞增殖迁移水平的影响.三磷酸腺苷(ATP)、乳酸和丙酮酸试剂盒用于检测ESCC细胞代谢水平.结果 SLC7A11蛋白表达定位于ESCC细胞的胞质,其在ESCC组织的表达水平高于癌旁正常组织(P<0.001).SLC7A11高表达的ESCC患者分化程度更差(P<0.01).Kaplan-Meier生存分析显示SLC7A11高表达的患者的生存时间明显短于低表达的患者(P<0.05).CCK-8实验和平板克隆形成实验表明,降低SLC7A11表达能够降低肿瘤细胞的增殖能力(P<0.001).Transwell实验显示SLC7A11表达水平降低,肿瘤细胞迁移能力下降(P<0.001).SLC7A11的表达水平降低时,ESCC细胞内ATP、乳酸和丙酮酸水平也随之下降(P<0.001),提示其与ESCC代谢相关.结论 ESCC组织中SLC7A11蛋白高表达水平较高,与患者预后不良密切相关.下调该蛋白表达显著抑制癌细胞的增殖与迁移.SLC7A11可能参与调控ESCC细胞的葡萄糖摄取、乳酸分泌和ATP代谢,从而影响ESCC的代谢微环境.
Objective To investigate the relationship between solute carrier family 7 member 11(SLC7A11)ex-pression in esophageal squamous cell carcinoma(ESCC)and clinical prognosis,and to determine its effects on ESCC cell growth,migration,and other biological activities.Methods SLC7A11 protein expression was mea-sured in 310 ESCC tissues and 259 adjacent normal tissues using immunohistochemistry to statistically assess the association of SLC7A11 with clinicopathologic characteristics and prognosis in ESCC patients.The expression of SLC7A11 in ESCC cell lines was suppressed through siRNA-mediated knockdown.The specific effects of SLC7A11 knockdown on proliferation and migration were evaluated using CCK-8,clonogenic assay,and Transwell assays.Adenosine triphosphate(ATP),lactic acid and pyruvate assays were used to measure ESCC metabolism.Results SLC7A11 protein expression was localized predominantly in the cytoplasm of ESCC tissues.Significantly higher SLC7A11 expression levels were observed in ESCC tissues compared to adjacent normal tissues(P<0.001).High SLC7A11 expression was associated with poorer differentiation in patients(P<0.01).Kaplan-Meier survival analy-sis demonstrated significantly shorter overall survival in patients with high SLC7A11 expression compared to those with low expression(P<0.05).CCK-8 and colony formation assays demonstrated that the knockdown of SLC7A11 expression significantly suppressed the proliferative capacity of tumor cells(P<0.001).Furthermore,Transwell assays revealed a marked decline in tumor cell migration capacity following SLC7A11 suppression(P<0.001).Critically,SLC7A11 knockdown also reduced intracellular levels of ATP,lactate,and pyruvate,demonstrating that SLC7A11 modulated metabolic activity in ESCC cells(P<0.001).Conclusion The expression level of SLC7A11 is relatively high in ESCC and is strongly associated with poor prognosis.Silencing SLC7A11 signifi-cantly inhibits esophageal cancer cell growth and migration.SLC7A11 has the ability to regulate glucose,lactic acid and ATP metabolism levels in ESCC,thereby affecting the metabolic microenvironment of ESCC.
张华坤;孙梦菲;孙琦;周紫如;禹洁;陈云昭;崔晓宾
石河子大学医学院病理学系,石河子 832002南京大学医学院附属鼓楼医院病理科,南京 210008南京大学医学院附属鼓楼医院病理科,南京 210008石河子大学医学院病理学系,石河子 832002浙江省人民医院,杭州医学院附属人民医院病理科,杭州 310014浙江省人民医院,杭州医学院附属人民医院病理科,杭州 310014石河子大学医学院病理学系,石河子 832002||南京大学医学院附属鼓楼医院病理科,南京 210008
医药卫生
SLC7A11ESCC增殖铁死亡肿瘤微环境葡萄糖代谢乳酸代谢ATP代谢
SLC7A11ESCCproliferationferroptosistumor microenvironmentglucose metabolismlactate metabolismATP metabolism
《安徽医科大学学报》 2026 (2)
270-276,7
国家自然科学基金项目(编号:82160542) Fund program National Natural Science Foundation of China(No.82160542)
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