HIF-1α Affects Fructose Metabolism in Colorectal Cancer Cells by Regulating GLUT5 Expression under Hypoxic Conditions
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-1α interfering 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-1α can promote the expression of GLUT5 in colorectal cancer cells,thereby enhancing the uptake of fructose,proliferation and invasion of CRC cells.
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