Synergistic augmentation of cisplatin-induced apoptosis in HeLa cells by rapamycin

Objective To evaluate the synergistic effect of rapamycin and cisplatin in cervical cancer cell line HeLa.Methods By using HeLa cells,cell proliferation was assessed by MTT assay after exposure to rapamycin,cisplatin,or both in combination.Apoptosis was analyzed by flow cytometry.Immunoblot analysis was performed to detect the expression of phosphorylated 4E-BP1 and S6 kinase 1.Results Rapamycin and cisplatin inhibited growth of HeLa cells in a time-dependent manner.Simultaneous exposure of cisplatin in combination with rapamycin resulted in a significantly synergistic antiproliferative effect.Rapamycin increased cisplatin-induced apoptosis in HeLa cells.Rapamycin inhibited the expression of phosphorylated 4E-BP1 and S6 kinase 1 in HeLa cells,and combined treatment with cisplatin inhibited the expression over that of rapamycin alone.Conclusion The results of the current study provide evidence of a synergistic relation between rapamycin and cisplatin in both inhibition of HeLa cells growth and induction of apoptosis.This suggests that rapamycin and cisplatin may be a rational combination of a targeted therapy for cervical cancer.