Synergistic Augmentation Of Cisplatin-induced Apoptosis In Hela Cells By Rapamycin

Objective Recent data suggested that the mammalian target of rapamycin (mTOR) play an important role in the tumorigenesis and development of malignant tumors.Rapamycin,a specific inhibitor of mTOR,is known to enhance the cytotoxicity of chemotherapeutic drugs.This study aimed 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 evaluated by flow cytometry. Immunoblot analysis was performed to assess expression of phosphorylation of 4E-BP1 and S6 kinase 1.Results Rapamycin and cisplatin inhibited growth in a time-dependent manner in Hela cell lines . Simultaneous exposure of cisplatin in combination with rapamycin resulted in a significant synergistic antiproliferative effect.Rapamycin increased cisplatin-induced apoptosis in Hela cells .Rapamycin inhibited expression of 4E-BP1 and S6 kinase 1 in Hela cells,and combined treatment with cisplatin inhibited expression over that of rapamycin alone.Conclusions 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. Objective Data suggested that PI-103 had powerful cytotoxic effects due to combinatorial inhibition of mTOR and PI3 kinase in malignant glioma.This study aimed to evaluate the influence of PI-103 on C13K cells proliferation,apoptosis and the growth of C13K cells xenografls in nude mice.Methods By using C13K cells, cell proliferation was assessed by MTT assay after exposure to PI-103, cisplatin, or both in combination. Apoptosis was evaluated by flow cytometry. Immunoblot analysis was performed to assess expression of phosphorylation of AKT and S6 kinase 1 .C13K cells was subcutaneously transplanted in to 16 nude mice,which were randomly divided into control group,PI-103 group,cisplatin group,combined treatment group,After corresponding treatments for 4 consecutive weeks,the tumor inhibition rate was evaluated。Results PI-103 in combination with cisplatin inhibited growth in a time-dependent manner in C13K cell lines .The inhibitory effect of combination therapy was superior to those treated with PI-103 and cisplatin alone.PI-103 increased cisplatin-induced apoptosis in C13K cells. PI-103 inhibited expression of phosphorylation of AKT and S6 kinase 1 in C13K cells.PI-103 plus cisplatin significantly inhibited the proliferation of xenografted C13K cells in nude mice,and there was significant differences between combined group and cisplatin group.Conclusions PI-103 enhanced growth inhibition of transplanted C13K cells by Cisplatin in nude mice.