Effects of Riboflavin Metabolic Pathways Combination with Cisplatin on Adhesion and Migration of Ovarian Cancer cells / 中国药学杂志

ABSTRACT

OBJECTIVE: To investigate the effects of interference of riboflavin (RIB) metabolic pathways on adhesion and migration to cisplatin (DDP) in ovarian cancer HO8910 cells. METHODS: Intervention RIB metabolic pathways by lentiviral vector harboring shRNA of riboflavin transporter 2 (RFT2) and chlorpromazine (CHL), a competitive inhibitor of RIB. HO8910 ovarian cancer cell line was divided into normal control group, shRNA control group, RFT2 shRNA group, CHL (50 μmol·L-1) group, DDP (20 μmol·L-1) group, RFT2 shRNA+DDP group, CHL + DDP group and DDP + RIB (20 μmol·L-1) group. Each group cells were collected after treatment 48 h according to the design. And then cell adhesive abilities were detected by adhesion experiment, the cells invasive abilities were observed by transwell method, the protein expressions of VEGF, MMP9 and MMP2 were detected by Western blot, and the expressions of TNF-α, NF-κB/p65 were assayed with laser confocal microscopy. RESULTS: Compared with the sole DDP treatment group, RFT2 shRNA or CHL combination with DDP had great advantages in reducing cell adhesion and migration viabilities, deceasing expressions of MM9 and MMP2, reducing cell expressions of TNF-α and NF-κB/p65. However, the RIB could weaken the effects of DDP on HO8910 cell. CONCLUSION: Interference metabolic pathway of RIB can enhance DDP effects on adhesion and migration viabilities of ovarian cancer HO8910 cell lines, and the effects are associated with blocking the pathway of TNF-α/NF-κB; However, RIB could attenuate the anti-tumor effects of cisplatin on HO8910 cell.