1. NVP-BEZ235 synergizes cisplatin sensitivity in osteosarcoma
- Author
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Min Wang, Qing-Chu Li, Zhifei Cui, Zhihai Su, Shui-Mu Chen, Lian-Jun Yang, Hong-Kai Lian, Hai Lu, Jin-Cheng Huang, Zheng-Bo Hu, Jinshi Liu, Jia-Yao Ouyang, and Bin Liu
- Subjects
0301 basic medicine ,autophagy ,cisplatin ,Cisplatin sensitivity ,chemotherapy ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,immune system diseases ,medicine ,PI3K/AKT/mTOR pathway ,Cisplatin ,Cell growth ,Chemistry ,Autophagy ,virus diseases ,osteosarcoma (OS) ,medicine.disease ,In vitro ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Osteosarcoma ,medicine.drug ,Research Paper - Abstract
Osteosarcoma(OS) remains a major health concern in childhood and adolescence, although cisplatin is one of the gold standard chemotherapeutic drugs in the treatment of OS, chemoresistant to cisplatin is common. Phosphoinositide 3-kinase (PI3K)-Akt-mammalian target of rapamycin inhibitor (mTOR) pathway and autophagy regulates chemosensitivity incancer cells. In this study, we hypothesized that NVP-BEZ235, a dual inhibitor of PI3K/mTOR, could synergize cisplatin sensitivity in OS. In vitro, NVP-BEZ235 plus cisplatinexerted a synergistic effect on cell proliferation inhibition and apoptosis induction. Cisplatin could activate PI3K-Akt-mTOR pathway activity in early times, whereas, NVP-BEZ235 could inhibit PI3K-Akt -mTOR pathway activity all the times alone or combined with cisplatin. What's more, NVP-BEZ235 could switch function of autophagy induced by cisplatin to synergize cisplatin sensitivity. In vivo, pronounced decrease in tumor cell proliferation and increase in apoptosisin combination-treated mouse xenograft models compared with cisplatin or NVP-BEZ235 treated models. All these results suggest NVP-BEZ235 could synergize cisplatin sensitivity in OS, combination of NVP-BEZ235 with cisplatin could represent a novel therapeutic strategy for treatment of OS.
- Published
- 2017