NVP-BEZ235 synergizes cisplatin sensitivity in osteosarcoma

Area of Science:

• Oncology
• Pharmacology

Background:

• Osteosarcoma (OS) is a significant childhood cancer with common resistance to cisplatin chemotherapy.
• The Phosphoinositide 3-kinase (PI3K)-Akt-mammalian target of rapamycin inhibitor (mTOR) pathway and autophagy are key regulators of cancer cell chemosensitivity.

Purpose of the Study:

• To investigate if NVP-BEZ235, a dual PI3K/mTOR inhibitor, can enhance cisplatin sensitivity in osteosarcoma.
• To explore the mechanistic effects of NVP-BEZ235 and cisplatin combination therapy on OS cells and tumor growth.

Main Methods:

• In vitro studies assessed the synergistic effects of NVP-BEZ235 and cisplatin on OS cell proliferation and apoptosis.
• In vivo studies utilized mouse xenograft models to evaluate the combination therapy's efficacy on tumor growth.
• Western blotting and autophagy assays were employed to analyze pathway activation and autophagy modulation.

Main Results:

• NVP-BEZ235 plus cisplatin demonstrated synergistic inhibition of OS cell proliferation and enhanced apoptosis in vitro.
• NVP-BEZ235 effectively inhibited the PI3K-Akt-mTOR pathway, while cisplatin activated it initially.
• NVP-BEZ235 modulated cisplatin-induced autophagy, contributing to synergistic chemosensitivity.
• Combination therapy significantly reduced tumor cell proliferation and increased apoptosis in vivo compared to single agents.

Conclusions:

• NVP-BEZ235 synergizes with cisplatin to enhance sensitivity in osteosarcoma.
• The combination of NVP-BEZ235 and cisplatin presents a novel therapeutic strategy for osteosarcoma treatment.
• Targeting the PI3K-mTOR pathway alongside conventional chemotherapy holds potential for improving OS outcomes.