Effects of galangin on proliferation,apoptosis and 5-FU resistance of colorectal cancer cells by regulating FOXO3-FOXM1 axis
- VernacularTitle:高良姜素调节FOXO3-FOXM1轴对结直肠癌细胞增殖、凋亡和5-FU耐药性的影响
- Author:
Liu YANG
1
;
Dan FENG
1
;
Li YANG
1
;
Ling TANG
1
;
Fei LUO
1
Author Information
- Publication Type:Journal Article
- Keywords: galangin; FOXO3-FOXM1 axis; colorectal cancer; proliferation; apoptosis; 5-fluorouracil; resistance
- From: Journal of Regional Anatomy and Operative Surgery 2025;34(1):5-10
- CountryChina
- Language:Chinese
- Abstract: Objective To investigate the effects of galangin on the proliferation,apoptosis,and 5-fluorouracil (5-FU) resistance of colorectal cancer (CRC) cells by regulating the FOXO3-FOXM1 axis. Methods CRC cells HCT8 and its drug-resistant cell lines HCT8/5-FU were cultured in vitro,and then treated with different concentrations (0,5,10,20,40 μmol/L) of galangin to screen experimental concentra-tions. HCT8 cells were divided into the ctrl group (without special treatment),NC group (transfected with empty plasmid),L-galangin group (treated with 10 μmol/L of galangin ),H-galangin group (treated with 20 μmol/L of galangin),and H-galangin+sh-FOXO3 group (trans-fected with FOXO3 shRNA plasmid after 20 μmol/L of galangin treatment). HCT8/5-FU cells were divided into the control group (without special treatment),5-FU+NC group (treated with empty plasmid after 5 μg/mL of 5-FU treatment),5-FU group (treated with 5 μg/mL of 5-FU),5-FU+L-galangin group (treated with 10 μmol/L of galangin after 5 μg/mL of 5-FU treatment),5-FU+H-galangin group (transfected with 20 μmol/L galangin after 5 μg/mL of 5-FU treatment),and 5-FU+H-galangin+sh-FOXO3 group (transfected with FOXO3 shRNA plasmid after 5 μg/mL of 5-FU and 20 μmol/L of galangin treatment). The cell proliferation ability was detected by CCK-8 assay;the cell clone formation ability was detected by clone formation assay;the cell apoptosis was detected by flow cytometry;the expression of related proteins were detected by Western blot.Results In HCT8 cells,compared with 0 μmol/L of galangin treatment,10,20,40 μmol/L of galangin treatment decreased the cell survival rate (P<0.05). In HCT8/5-FU cells,compared with 0 μmol/L galangin treatment,40 μmol/L of galangin treatment decreased the cell survival rate (P<0.05). After 10 and 20 μmol/L of galangin treatment,the apoptosis rate,and the expression of FOXO3 and Bax proteins were increased (P<0.05),while cell survival rate,clone formation number,and expression of FOXM1 and PCNA proteins decreased in HCT8 and HCT8/5-FU cells (P<0.05),and the MRP-1 protein expression in HCT8/5-FU cells decreased (P<0.05). Knocking down sh-FOXO3 could attenuate the effects of high dose of galangin on HCT8 and HCT8/5-FU cells (P<0.05). Conclusion Galangin may inhibit the proliferation,promote apoptosis,and reduce 5-FU resistance of CRC cells by regulating the FOXO3-FOXM1 axis.
