The effects of FANCFon paclitaxel-resistant triple negative breast cancercell / 中国肿瘤生物治疗杂志

ABSTRACT

@#[Abstract] Objective: To establish paclitaxel(PTX)-resistant human triple negative breast cancer cell line and to examine the expression profile of FA-related genes and FANCF, the correlation between the expression of FA-related genes, FANCF and PTX-resistance in breast cancer were further analyzed. Methods: PTX-resistant MDA-MB-231 cell line was established by means of long-term PTX-exposed culture. The sensitivity of the cells to paclitaxel was determined by the CCK8 assay. The cell cycle distribution was examined by flow cytometry after exposure to the paclitaxel. The expression of FA-related gene mRNA and FANCF protein were examined by using real time quantitative PCR and Western blotting. The expression of FANCF in the cells was reduced by RNAi interference technology and the effect of the RNAi was verified. Results: MDA-MB-231/PTX cell showed a 9.9-fold resistance to paclitaxel, indicating that the cell had acquired resistance to PTX. PTX treatment significantly induced G0/G1 arrest and the number of cells in phase S markedly decreased after exposure to PTX. The mRNA and protein expression of FANCF was significantly higher in PTX-resistant cell than that in PTX-sensitve parental cell，Knockdown of FANCF induced apoptosis in MDA-MB-231/PTX cell as well as in parental cell. FANCF knockdown increased the sensitivity of paclitaxel to both MDA-MB-231 and MDA-MB-231/PTX cells (P<0.05 or P<0.01). Conclusion: FANCF played an important role in PTX resistance of the breast cancer cells and FANCF might be a target for therapy aimed at reversing chemoresistance.