Study of the Alendronate inhibiting growth and inducing apoptosis of giant cell tumor of bone in vitro / 中国矫形外科杂志

ABSTRACT

[Objective]Giant cell tumor of bone is notorious for its local aggressive behavior and its tendency to recur after operative treatment.Bisphosphonates is the drug of anti-osteoporosis.It is found also have anti-cancer effect recently.We conducted experiment examing the effect of bisphosphonates alendronate on the growth and survival of the cells.To study if bisphosphonates are capable of inducing cells death and significantly inhibiting their growth in vitro.[Method]Cells viability was detected by MTT Assay after the tumor cells were cured with different concentration and different time.Tumor cells apoptosis with in situ TUNEL assay and flow cytometry was detected.The active Caspase-3 was also detected.[Result]After exposure to alendronate,the cells exhibited the characteristic features of cell shrinkage,rounding and partial detachment,and demonstrated the lobulated appearance of apoptotic cells.It was much more prominent while the treating time prolonged or the concentration increased.Alendronate((5 200) M) treatment for 24 h,resulted in 2.79%~31.17% decrease in cell viability,and 11.13%~49.94% for 72 h,respectively.A significant dose-dependent and time-dependent decrease in the number of viable cells was observed in the GCT cells.After Alendronate treat for 24 h,the mean cell population in apoptosis was 14.32% at concentration 5 mmol/l,and 40.24% at 200 mmol/l.It was up to 18.41% and 42.22% respectively after 48 h.In Alendronate-treated GCT cells,Caspase-3 activation was observed.The cell response varied with doses of Alendronate showing the levels of Caspase-3 expression with a dose dependent response.[Conclusion]In conclusion,we demonstrated that bisphosphonate alendronate could inhibit GCT cells in the present study.This response was time-dependent and dose-dependent.Alendronate inducing apoptosis in GCT cells is mediated by the activation of Caspase-3.