OncotargetJul 28, 2015

OSI-027 slows pancreatic cancer cell growth and improves gemcitabine treatment effectiveness in lab and animal tests

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 3, 2026

Abstract

OSI-027 significantly arrested the cell cycle in the G0/G1 phase and inhibited the proliferation of multiple pancreatic ductal adenocarcinoma cell lines.

OSI-027 is a selective inhibitor that targets mTORC1 and mTORC2.
The treatment downregulated several key proteins associated with cell growth and survival, including phospho-Akt and cyclin D1.
Combination treatment with OSI-027 and gemcitabine enhanced apoptosis in Panc-1, BxPC-3, and CFPAC-1 cells.
The combination showed synergistic cytotoxic effects in both cell cultures and a mouse model of PDAC.
OSI-027 also reduced levels of multidrug resistance (MDR)-1, which is linked to chemotherapy resistance.

Simplified

Despite its relative rarity, pancreatic ductal adenocarcinoma (PDAC) accounts for a large percentage of cancer deaths. In this study, we investigated the in vitro efficacy of OSI-027, a selective inhibitor of mammalian target of rapamycin complex 1 (mTORC1) and mTORC2, to treat PDAC cell lines alone, and in combination with gemcitabine (GEM). Similarly, we tested the efficacy of these two compounds in a xenograft mouse model of PDAC. OSI-027 significantly arrested cell cycle in G0/G1 phase, inhibited the proliferation of Panc-1, BxPC-3, and CFPAC-1 cells, and downregulated mTORC1, mTORC2, phospho-Akt, phospho-p70S6K, phospho-4E-BP1, cyclin D1, and cyclin-dependent kinase 4 (CDK4) in these cells. Moreover, OSI-027 also downregulated multidrug resistance (MDR)-1, which has been implicated in chemotherapy resistance in PDAC cells and enhanced apoptosis induced by GEM in the three PDAC cell lines. When combined, OSI-027 with GEM showed synergistic cytotoxic effects both in vitro and in vivo. This is the first evidence of the efficacy of OSI-027 in PDAC and may provide the groundwork for a new clinical PDAC therapy.

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OSI-027 slows pancreatic cancer cell growth and improves gemcitabine treatment effectiveness in lab and animal tests

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