异鼠李素对口腔鳞状细胞癌细胞增殖和糖酵解影响的研究  

Study of the Effects of Isorhamnetin on Proliferation and Glycolysis of Oral Squamous Cell Carcinoma Cells

作　　者：廖金庄 谢李 张俊卿 王基栋 LIAO Jinzhuang;XIE Li;ZHANG Junqing;WANG Jidong(Department of Radiology,The Third Xiangya Hospital,Central South University,Changsha 410013,Hunan,China;Department of Head and Neck Surgery,Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine,Central South University,Changsha 410013,Hunan,China;Changde Hospital,Xiangya School of Medicine,Central South University(The First People’s Hospital of Changde City),Changde 415000,Hunan,China)

机构地区：[1]中南大学湘雅三医院放射科,中国湖南长沙410013 [2]湖南省肿瘤医院/中南大学湘雅医学院附属肿瘤医院头颈外科,中国湖南长沙410013 [3]中南大学湘雅医学院附属常德医院(常德市第一人民医院),中国湖南常德415000

出　　处：《生命科学研究》2024年第4期283-288,295,共7页Life Science Research

基　　金：湖南省自然科学基金医卫行业联合基金项目(2024JJ9261)。

摘　　要：为探讨异鼠李素(isorhamnetin)对人口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)(简称口腔鳞癌)细胞增殖以及糖酵解的影响,给予不同剂量异鼠李素处理口腔鳞癌细胞系CAL27和SCC9,并采用细胞活力分析和软琼脂集落实验检测异鼠李素对口腔鳞癌细胞增殖的影响;借助糖酵解分析实验检测异鼠李素对口腔鳞癌细胞乳酸产生和葡萄糖消耗的影响;利用蛋白质印迹法明确异鼠李素对口腔鳞癌细胞糖酵解相关信号通路的调控;最后,通过异种移植瘤模型验证异鼠李素在体内对肿瘤的影响。体外实验结果显示,异鼠李素以剂量依赖的方式抑制CAL27和SCC9细胞的增殖与糖酵解,并且这种抑制作用与糖酵解关键限速酶己糖激酶2(hexokinaseⅡ,HK2)而不是磷酸果糖激酶(phosphofructokinase,PFK)和丙酮酸激酶M2(pyruvate kinase M2,PKM2)的抑制有关。体内结果表明,异鼠李素抑制了口腔鳞癌在体内的生长,并降低了肿瘤组织中Ki67和HK2的表达。总的来说,研究结果表明,异鼠李素可抑制口腔鳞癌的增殖与糖酵解,且这种抑制效应与HK2表达降低有关。To investigate the effects of isorhamnetin on human oral squamous cell carcinoma(OSCC)cells,the impact of different doses of isorhamnetin on the proliferation of OSCC cell lines CAL27 and SCC9 was detected using both cell viability and colony formation assays,and the effect of isorhamnetin on lactate production and glucose consumption in OSCC cells was determined by glycolysis assay.The changes in glycolysis-related signaling pathways after treatment with different doses of isorhamnetin were examined through immunoblotting method.Finally,the xenograft mouse model was used to validate the in vivo inhibitory effect of isorhamnetin on tumors.The in vitro experiments showed that isorhamnetin dose-dependently inhibited the proliferation and glycolysis of CAL27 and SCC9 cells,and this inhibitory effect was related to the suppression of key glycolysis rate-limiting enzyme hexokinaseⅡ(HK2)rather than phosphofructokinase(PFK)and pyruvate kinase M2(PKM2).The in vivo experiments demonstrated that isorhamnetin inhibited the growth of OSCC and reduced the expression of Ki67 and HK2 in tumor tissue.Overall,the results suggest that isorhamnetin inhibits the proliferation and glycolysis of OSCC,and the inhibitory effect is associated with the downregulation of HK2 expression.

关 键 词：口腔鳞状细胞癌(OSCC) 异鼠李素 细胞增殖 糖酵解 己糖激酶2(HK2) 

分 类 号：Q25[生物学—细胞生物学] R739.85[医药卫生—肿瘤]