缺氧条件下HIF-1α通过调节GLUT5的表达影响结直肠癌细胞果糖代谢  

HIF-1αAffects Fructose Metabolism in Color ectal Cancer Cells by Regulating GLUT5 Expression under Hypoxic Conditions

作　　者：江现丽 江小丽 魏聘[1] 杨学丽[1] 姜琳娜[1] 安欣[1] 吴倩岚[1] JIANG Xian-li;JIANG Xiao-li;WEI Ping;YANG Xue-li;JIANG Lin-na;AN Xin;WU Qian-lan(Department of Pathology,Handan City First Hospital;Department of Pathology,Handan City Sixth Hospital,Handan 056800,China)

机构地区：[1]邯郸市第一医院病理科 [2]邯郸市第六医院病理科,河北邯郸056800

出　　处：《南昌大学学报（医学版）》2024年第6期50-54,61,共6页Journal of Nanchang University：Medical Sciences

基　　金：河北省卫健委医学科学研究课题计划项目(20231902)。

摘　　要：目的探究缺氧条件下缺氧诱导因子-1α(HIF-1α)对结直肠癌(CRC)细胞果糖代谢的影响及可能机制。方法用慢病毒转染CRC细胞系SW480,构建敲低组(转染含HIF-1α干扰质粒的慢病毒)和对照组(转染含空白质粒的慢病毒),用蛋白免疫印迹和qRT-PCR实验验证转染效率。将2组细胞置于缺氧条件下培养,通过细胞克隆形成实验检测细胞增殖能力,Transwell实验检测细胞侵袭迁移能力;分别在第24、48和72 h使用果糖含量检测试剂盒测定2组培养基上清中剩余的果糖含量并使检测2组细胞内葡萄糖转运蛋白5(GLUT5)的表达水平。结果低氧条件下,敲低组形成的集落数显著少于对照组(P<0.0001),敲低组穿过Matrigel胶的细胞数量显著少于对照组(P<0.01),敲低组培养基上清液中剩余的果糖水平显著高于同时期的对照组(24 h时比较P<0.001,48 h时比较P<0.0001,72 h时比较P<0.0001),且敲低组GLUT5的表达量显著低于对照组(P<0.0001)。结论缺氧条件下,HIF-1α能够促进结直肠癌细胞中GLUT5的表达,增强CRC细胞的增殖、侵袭以及摄取果糖的能力。Objective To explore the impact of hypoxia-inducible factor-1α(HIF-1α)on fructose metabolism in colorectal cancer(CRC)cells under hypoxic conditions and its potential mechanism.Methods The CRC cell line SW480 was transfected with lentivirus to construct a knockdown group(transfected with lentivirus containing HIF-1αinterfering plasmid)and a negative control group(transfected with lentivirus containing blank plasmid).Western blotting and qRT-PCR experiments were conducted to verify the transfection efficiency.The SW480 cells in the 2 groups were cultured under hypoxic conditions;the proliferation of SW480 cells was detected by colony formation test,and the invasion and migration of SW480 cells was evaluated by Transwell test;the residual fructose content in the supernatant of the 2 culture media groups was measured at 24,48,and 72 hours using fructose content detection kit,and the expression level of glucose transporter 5(GLUT5)in SW480 cells was detected in both groups.Results Under hypoxic conditions,the number of colonies formed in the knockdown group was significantly less than that in the control group(P<0.0001).The number of cells passing through Matrigel gel in the knockdown group was significantly lower than that in the control group(P<0.01).The residual fructose level in the supernatant of the culture medium of the knockdown group was significantly higher than that of the control group at the same time point(P<0.001 at 24 h,P<0.0001 at 48 h,and P<0.0001 at 72 h).The expression level of GLUT5 in the knockdown group was significantly lower than that in the control group(P<0.0001).Conclusion Under hypoxic conditions,HIF-1αcan promote the expression of GLUT5 in colorectal cancer cells,thereby enhancing the uptake of fructose,proliferation and invasion of CRC cells.

关 键 词：缺氧诱导因子1Α 结直肠癌 葡萄糖转运蛋白5 果糖代谢 

分 类 号：R735.34[医药卫生—肿瘤]