6-shogaol enhances the chemosensitivity of drug-resistant colon cancer cell line SW620/5-Fu by inactivating the SDF-1α/CXCR7 signaling pathway

ZHAO Xiaohua; GUO Hua

doi:10.3969/j.issn.1002-7386.2025.06.005

Abstract：Objective To investigate the effect of 6-shogaol on the chemosensitivity of drug-resistant colon cancer(CC)cell line SW620/5-Fu to 5-Fu and its mechanism.Methods Drug-resistant cell line SW620/5-Fu was created,and induced with 6-shogaol at gradient concentrations(0,5,10,20,40 and 80μmol/L).The cell counting kit-8(CCK-8)assay was performed to detect cell viability and calculated the half-maximal inhibitory concentration(IC50)value against 5-Fu.Flow cytometry was performed to examine cell cycle progression and apoptosis.Western blot was performed to detect protein levels of senescence-associated factors p21 and p53.The quantitative reverse transcriptase polymerase chain reaction(qRT-PCR)was performed to detect mRNA levels of senescence-associated secretory factors interleukin 6(IL-6)and IL-8.A nude mice xenograft colon cancer model was created to validate the anti-cancer effect of 6-shogaol in vivo.Immunochemistry was performed to detect positive expressions of p21,p53,Ki67 and cleaved Caspase 3.Results 6-shogaol treatment significantly increased the chemosensitivity of SW620/5-Fu cells to 5-Fu,increased the proportion of cells in the G0/G1 phase(P＜0.05)and induced cell apoptosis.6-shogaol treatment significantly reduced cellular senescence,manifesting as downregulations of p21,p53,IL-6 and IL-8(P＜0.05).In addition,6-shogaol significantly downregulated stromal-derived factor-1 alpha(SDF-1α)and C-X-C motif chemokine receptor 7(CXCR7)in SW620/5-Fu cells(P＜0.05).In vivo experimental results showed that 6-shogaol treatment significantly inhibited the growth of colon cancer in nude mice.Conclusion 6-shogaol inhibits senescence-mediated 5-Fu resistance in SW620/5-Fu cells by negatively regulating the SDF-1α/CXCR7 signaling pathway.This study provides a promising treatment strategy for improving the efficacy of 5-Fu chemotherapy for colon cancer.