吡非尼酮对三阴性乳腺癌4T1细胞增殖、迁移和侵袭影响的机制研究OA

Objective:To explore the effects of of pirfenidone(PFD)on the proliferation,migration,and invasion abilities of triple-negative breast cancer 4T1 cells and its mechanisms.Methods:The triple-negative breast cancer 4T1 cell line was cultured.The 4T1 cells treated with different concentrations of PFD(2,4,6,and 8 mmol/L)were taken as the drug treatment group,and the 4T1 cells not treated with PFD were taken as the control group.The expression of arylamine N-acetyltransferase 1(NAT1)protein was detected by Western blot.The effect of PFD on 4T1 cells' proliferation ability was detected by CCK-8 assay and clone formation assay.The scratch assay and Transwell migration assay were used to detect the effect of PFD on 4T1 cells' migration ability.The Transwell invasion assay was used to detect the effect of PFD on 4T1 cells' invasion ability.Molecular docking was used to verify the interaction between PFD and NAT1.Results:Compared to the control group,PFD significantly inhibited the protein expression of NAT1 at the concentration of 8 mmol/L(P<0.000 1);Compared to the control group,the proliferation,migration,and invasion abilities of 4T1 cells treated with PFD at 2,4,6 and 8 mmol/L gradually weakened in a concentration-dependent manner.Among them,when the concentration of PFD was 8 mmol/L,it significantly inhibited the proliferation,migra-tion,and invasion abilities of 4T1 cells(P<0.001);Furthermore,molecular docking indicated that there were hydrogen bonds and hydrophobic interactions between PFD and NAT1.Conclusion:The concentration of PFD at 8 mmol/L reduces the prolifera-tion,migration,and invasion abilities of triple-negative breast cancer 4T1 cells by inhibiting the expression of NAT1 protein.