Growth Inhibiting Effect Of Flavopiridol Combined With Cisplatin On Human Cancer Cell Line U2-OS

Objective:To study effects of flavopiridol, cisplatin, and flavopiridol combined with cisplatin on human cancer cell line U2-OS, and testify whether flavopiridol can be used as an ancillary drug of human osteoscarcome.Methods:First, the human osteoscarcome U2-OS cells at logarithmic phase were treated with vehicle DMSO or flavopiridol at different concentrations (50,100,200, 400 and 1000 nmol/L) for different time. The cell viability was assayed 48 hr later using MTT and the inhibitory rate of cell prolofication and IC50 of flavopiridol were calculated. After that, the U2-OS cells were treated with vehicle DMSO, flavopiridol or cisplatin only and flavopiridol combined with cisplatin, the inhibitory rate of cell proliferation were detemined using MTT at different time points (2,6,12,24 and 48hr). Cell apoptosis was measured by flow cytometry after the treatment with flavopiridol at different concentrations (0,100,200,340 and 400 nmol/L) for 48hr. Also, cell apoptosis was measured after the treatment with DMSO, flavopiridol or cisplatin only and flavopiridol combined with cisplatin for 48hr.Results:The proliferation of U2-OS cell was inhibited by flavopiridol, the IC50 of Flavopiridol was 340 nmol/L. Inoculation cells 24 hour, the inhibitory rate was not high and the inhibite of cell grow were not manifest in statistics. When cells were incubated with flavopiridol at 50,100,200,400 and 1000 nmol/L for 48 hr, the inhibitory rate was 20.59±3.15%,31.39±3.52%,41.41±1.41%,52.21±2.69%, and 68.86±1.20%, respectively. The inhibitory rate was increased with the concentration of flavopiridol (P<0.05). Furthermore, compared with treatment with flavopiridol or cisplatin only, the inhibitory rate was increased by treatment with flavopiridol plus cisplatin, the difference of inhibitory ratio was significant (P<0.05). When the cells were treated with flavopiridol at 0,100,200,340,400 nmol/L for 48 hr, the apoptotic cells were 3.60%,7.13%,19.40%,38.90%,42.49%, respectively. The apoptosis was increased with the drugs concentration. The apoptotic cells in the combined treatment were more than those in solo treatment. When the cells were treated with the drugs at flavopiridol, cisplatin, flavopiridol combined with cisplatin and control group for 48 hr, the apoptotic ratio was 13.03%,38.90%,56.11% and 2.28%, respectively. Compared with cisplatin treatment, the G1 phase were arrested in the combined treatment of flavopiridol plus cisplatin. Moreover, compared with flavopiridol treatment, the G1 phase was arrested and S phase was increased in the combined treatment of flavopiridol plus cisplatin.Conclusions:Flavopiridol can restrain the growth of human cancer cell line U2-OS and induce their apoptosis. Flavopiridol and cisplatin had synergetic effect on inhibition of U2-OS cells. Flavopiridol can enhance U2-OS cells sensitivity to cisplatin significantly.