FoxM1 inhibitor sensitize resistant osteosarcoma cells to cisplatin by down-regulation of Rad51 / 临床与实验病理学杂志

ABSTRACT

Purpose To investigate whether FoxM1 participate in inhibitory effect of cisplatin (CDP) in resistant osteosarcoma cell lines by down-regulation of Rad51.Methods The resistant osteosarcoma cell lines were induced by gradually increasing dose intermittent action,and were named MG-63/R and HOS-MNNG/R respectively.The mRNA and protein level of FoxMl and Rad51 were detected by qRT-PCR and Western blot analysis in resistant cells and parental cells.The mRNA and protein level of FoxM1 and Rad51 were detected by qRT-PCR and Western blot analysis in resistant cells after treatment of 4 μmol/L Thiostrepton.The effect of single or combined treated of 4 tμmol/L Thiostrepton or 2 tμg/mL CDP on the rate of cell proliferation in resistant cells was examed by cell counting.Results Resistant osteosarcoma cell lines MG-63/R and HOSMNNG/R were established and stablely growthed in the concentration of 2 μg/mL CDP,and the resistance index was 30.52 and 37.87 respectively (severe CDP resistance).The mRNA and protein level of FoxM1 and Rad51 were significantly increaced in resistant cells compared with parental cells.The proliferation rate of resistant cells in conbination of 4 μmol/L Thiostrepton and 2 μg/mL CDP treated group was significantly lower than these two drugs single treated group.The level of mRNA and protein of FoxM1 and Rad51 were significantly decreased after 4 μmol/L Thiostrepton treatment in CDP resistant cells.Conclusion The results suggest that FoxM1 and Rad51 may participate in the resistant osteosarcoma cells to CDP.FoxM1 inhibitor Thiostrepton may strengthen the inhibitory effect of CDP in the resistant cells by down-regulation of Rad51.