特异性靶向葡萄糖转运-1抑制药(STF-31)通过影响人睾丸癌细胞I-10线粒体功能对介导细胞死亡的作用  

Effect of specific targeting glucose transporter inhibitor(STF-31)on the mediated cell death through affects I-10 mitochondrial function of human testicular cancer cells

作　　者：姚越 张冲 韩兵 汤玉锐 熊言骏 汪盛[1] YAO Yue;ZHANG Chong;HAN Bing;TANG Yu-rui;XIONG Yan-jun;WANG Sheng(Department of Urology,The First Affiliated Hospital of Bengbu Medical College,Bengbu 233000,Anhui Province,China)

机构地区：[1]蚌埠医学院第一附属医院泌尿外科,安徽蚌埠233000

出　　处：《中国临床药理学杂志》2021年第14期1816-1819,共4页The Chinese Journal of Clinical Pharmacology

基　　金：安徽省自然科学基金资助项目(1808085MH293);蚌埠医学院2020科研创新计划基金资助项目(Byycx20030)。

摘　　要：目的从线粒体功能方面探究特异性靶向葡萄糖转运-1抑制药(STF-31)对人睾丸癌细胞I-10凋亡的影响。方法向I-10细胞分别加入低、中、高3个浓度(4,8,16μmol·L^(-1))的STF-31作为实验组,空白对照组加入等量培养基。用活性氧试剂盒检测细胞线粒体功能变化,四甲基偶氮唑盐法检测细胞增殖抑制率,碘化丙啶双染法检测细胞凋亡率,蛋白质印迹法检测线B淋巴细胞白血病/淋巴瘤-2(Bcl-2)蛋白、Bcl-2相关X蛋白(Bax)、裂解半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)和自噬相关蛋白(LC3-Ⅱ/LC3-Ⅰ)相对表达水平。结果STF-31可随时间剂量依赖性的抑制I-10细胞增殖,低、中、高3个浓度实验组24,48,72 h的细胞IC50分别为21.3,8.01和4.13μmol·L^(-1)。空白对照组与低、中、高3个浓度实验组24 h细胞凋亡率分别为(4.93±0.54)%,(9.95±1.26)%,(26.70±3.11)%和(68.00±3.42)%;这4组的Bax蛋白相对表达量分别为0.10±0.04,0.32±0.06,0.53±0.11,0.71±0.04;这4组的Bcl-2蛋白相对表达量分别为0.42±0.03,0.25±0.24,0.12±0.14,0.05±0.18;这4组的cleaved caspase 3蛋白相对表达量分别为0.41±0.06,0.53±0.12,0.76±0.07,0.91±0.04;这4组的LC3-Ⅱ/LC3-Ⅰ蛋白相对表达量分别为0.81±0.04,2.30±0.11,2.70±0.09,3.60±0.07。上述指标:低、中、高3个浓度实验组与空白对照组比较,差异均有统计学意义(均P<0.05)。结论STF-31对睾丸癌细胞I-10具有增殖抑制及诱导凋亡和增加自噬作用,其机制可能为STF-31影响I-10细胞线粒体功能。Objective To explore the effect of specific targeting glucose transport-1 inhibitor(STF-31)on the apoptosis of human testicular cancer cell I-10 from the aspect of mitochondrial function.Methods Three concentrations of STF-31(4,8,16μmol·L^(-1))were added to I-10 cells respectively as the experimental group,the blank control group was added with the same amount of medium.The reactive oxygen species kit was used to test changes in cell mitochondrial function.Tetramethylazolium salt method was used to detect cell proliferation inhibition rate.Propidium iodide double staining method was used to detect cells apoptosis rate.Western blotting was used to detect B cells lymphocytic leukemia/lymphoma-2(Bcl-2)protein,Bcl-2 related X protein(Bax),and lytic caspase-3(Caspase-3)and autophagy-related protein LC3-Ⅱ/LC3-Ⅰrelative expression levels.Results STF-31 could inhibit the proliferation of I-10 cells in a dose-dependent manner over time.The IC50 of cells at 24,48 and 72 h in the low,medium and high concentration groups were 21.3,8.01 and 4.13μmol·L^(-1),respectively.The 24 h cell apoptosis rate of the blank control group and the low,medium and high concentration experimental groups were(4.93±0.54)%,(9.95±1.26)%,(26.70±3.11)%,(68.00±3.42)%,respectively;the relative expression levels of Bax in the 4 groups were 0.10±0.04,0.32±0.06,0.53±0.11,0.71±0.04,respectively;the relative expression of Bcl-2 in the 4 groups were 0.42±0.03,0.25±0.24,0.12±0.14,0.05±0.18,respectively;the relative expression levels of cleaved caspase 3 in the 4 groups were 0.41±0.06,0.53±0.12,0.76±0.07,0.91±0.04,respectively;the relative expression levels of LC3-Ⅱ/LC3-Ⅰin the 4 groups were 0.81±0.04,2.30±0.11,2.70±0.09,3.60±0.07,respectively.Comparison between the low,medium and high dose experimental groups and the blank group,the difference of the factors were statistically significant(all P<0.05).Conclusion STF-31 can inhibit the proliferation of testicular cancer cell of I-10 and induce apoptosis and increase autophagy,the

关 键 词：睾丸癌 特异性靶向葡萄糖转运-1抑制药 线粒体功能 凋亡 自噬 

分 类 号：R97[医药卫生—药品]