SDF-1α/CXCR7 mediating colon carcinoma cells resistant to 5-FU / 肿瘤

ABSTRACT

Objective: To investigate the effects of stromal cell-derived factor-1α (SDF-1α)through CXC-domain chemokine receptor 4 (CXCR4) and CXCR7 on colonic cancer cells resistant to 5-fluorouracil (5-FU), and to explore its possible mechanism. Methods: The expression levels of CXCR4 and CXCR7 in colonic cancer SW480, SW620, HCT116 and HT29 cells were detected by Western blotting. After treatment with SDF-1α, SDF-1α in combination with AMD3100 (CXCR4 inhibitor) or SDF-1α in combination with anti-CXCR7 monoclonal antibody for 6 hours, the SW480 and HT29 cells were then treated with 3.1, 6.25, 12.5, 25, 50, 100 and 150 μg/mL 5-FU for 48 hours. The half inhibitory concentration (IC50) value of 5-FU was detected by sulforhodamine B (SRB) assay. The expressions of drug-resistant proteins P-glycoprotein (P-gp) and multidrug resistance protein-1 (MRP-1) were detected by Western blotting. Results: The expression levels of CXCR4 and CXCR7 in SW480 and HT29 cells were higher than those in SW620 and HCT116 cells (all P 0.05). The expression levels of P-gp in SW480 and HT29 cells in group of SDF-1α in combination with anti-CXCR7 monoclonal antibody were lower than those in SDF-1α group (both P 0.05). The expression level of MRP-1 had no significant difference among different groups (P > 0.05). Conclusion: SDF-1α can promote the resistance to 5-FU in colonic cancer cells. This effect may be related to up-regulating the expression level of P-gp through SDF-1α/CXCR7 signal pathway.