CXCL-1促进胃癌细胞迁移和侵袭机制探讨

Effect of CXCL1 on gastric cancer cells migration and invasion

OBJECTIVE Cancer associated fibroblasts (CAFs)are important cells in the tumor microenvironment, which play vital roles in the initiation and progression of tumor.The study aimed to investigate the effects and molecular mechanism of CXCL1 secreting from cancer-associated fibroblast on gastric cancer cells migration and invasion.METH-ODS Isolated and primary cultured CAFs and normal fibroblasts (NFs).To determine the CXCL1 mRNA and protein expression level using RT-PCR and Western blot assay,and determined CXCL1 concentration in CAFs-CM (conditioned media)and NFs-CM using ELISA assay.We further investigated the effects of exogenous CXCL1 and CXCL1 antibody on the migration and invasion of gastric cancer cells using Transwell and healing assay.We determined the effects of exog-enous CXCL1 and CXCL1 antibody on the expression level of MMP-3 protein via Western blot assays.RESULTS The relative expression levels of CXCL1 mRNA and protein in CAFs and secretion concentration of CXCL1 in CAFs-CM were significantly higher than that of NFs and NFs-CM (P <0.01).The number of cells penetrated membrane and wound clo-sure rate of CXCL1 group were significantly more and lower than that of the control group (t = 3.213,P =0.030;t =3.006,P =0.040),respectively.The number of cells penetrated membrane and wound closure rate of CXCL1 antibody group were significantly higher than that of control group (t=3.811,P =0.020;t =4.678,P =0.010).The expression level of MMP-3 protein is up-regulated in gastric cancer in exogenous CXCL1 group and down regulated in CXCL1 anti-body group (t=4.153,P =0.009;t=3.349,P =0.030).CONCLUSION CXCL1 secreting from CAFs promotes the mi-gration and invasion of gastric cancer cells probably by regulating MMP-3 protein.