Astragali Radix-Curcumae Rhizoma inhibits colon cancer progression and enhances 5-FU efficacy by regulating hypoxia-inducible factors and tumor stem cells
The animal and cell models were used in this study to investigate the mechanism of Astragali Radix-Curcumae Rhizoma(HQEZ)in inhibiting colon cancer progression and enhancing the efficacy of 5-fluorouracil(5-FU)by regulating hypoxia-inducible factors and tumor stem cells.The animal model was established by subcutaneous transplantation of colon cancer HCT116 cells in nude mice,and 24 successfully modeled mice were randomized into model,5-FU,HQEZ,and 5-FU+HQEZ groups.The tumor volume was measured every two days.Western blot was employed to measure the protein levels of epidermal growth factor receptor(EGFR),dihy-dropyrimidine dehydrogenase(DPYD),and thymidylate synthase(TYMS),the key targets of the hypoxic core region,as well as the hypoxia-inducible factors HIF-1α and HIF-2α and the cancer stem cell surface marker CD133 and SRY-box transcription factor 2(SOX2).The results of animal experiments showed that HQEZ slowed down the tumor growth and significantly increased the tumor in-hibition rate of 5-FU.Compared with the model group,HQEZ significantly down-regulated the protein levels of EGFR and DPYD,and 5-FU+HQEZ significantly down-regulated the protein levels of EGFR and TYMS in tumors.Compared with the model group,HQEZ significantly down-regulated the protein levels of HIF-1α,HIF-2α,SOX2,and CD 133 in the hypoxic core region.Compared with the 5-FU group,5-FU+HQEZ lowered the protein levels of HIF-1α,HIF-2α,and SOX2.The cell experiments showed that the protein le-vels of HIF-1α and HIF-2α in HCT116 cells elevated significantly after low oxygen treatment.Compared with 5-FU(1.38 μmol·L-1)alone,HQEZ(40 mg·mL-1)and 5-FU+HQEZ significantly down-regulated the protein levels of HIF-1α,HIF-2α,and TYMS.In conclusion,HQEZ can inhibit the expression of hypoxia-responsive molecules in colon cancer cells and reduce the properties of cancer stem cells,thereby enhancing the therapeutic effect of 5-FU on colon cancer.
Astragali Radix-Curcumae Rhizomaherb pairhypoxia-inducible factorstumor stem cellcolon cancer
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