ArticleOncotarget2015
OSI-027 inhibits pancreatic ductal adenocarcinoma cell proliferation and enhances the therapeutic effect of gemcitabine both in vitro and in vivo.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Carrier-Free Nanoassembly Suppresses Phase Separation via Ribosome-Inspired Crowding Control for Enhanced Chemo-Immunotherapy.ACS nano · 2026Article
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- Roles of Rictor alterations in gastrointestinal tumors (Review).Oncology reports · 2024Article
- Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease.Signal transduction and targeted therapy · 2023Review
- mTOR as a Potential Target for the Treatment of Microbial Infections, Inflammatory Bowel Diseases, and Colorectal Cancer.International journal of molecular sciences · 2022Review
- Functional stratification of cancer drugs through integrated network similarity.NPJ systems biology and applications · 2022Article
- Combating TKI resistance in CML by inhibiting the PI3K/Akt/mTOR pathway in combination with TKIs: a review.Medical oncology (Northwood, London, England) · 2021Review
- Mitochondrial Genome-Derived circRNA mc-COX2 Functions as an Oncogene in Chronic Lymphocytic Leukemia.Molecular therapy. Nucleic acids · 2020Article
- The role of RICTOR amplification in targeted therapy and drug resistance.Molecular medicine (Cambridge, Mass.) · 2020Review
- High Expression of Long Noncoding RNA HOTAIRM1 is Associated with the Proliferation and Migration in Pancreatic Ductal Adenocarcinoma.Pathology oncology research : POR · 2019Article
- Gemcitabine enhances OSI-027 cytotoxicity by upregulation of miR-663a in pancreatic ductal adenocarcinoma cells.American journal of translational research · 2019Article
- Mechanisms of autophagy and relevant small-molecule compounds for targeted cancer therapy.Cellular and molecular life sciences : CMLS · 2018Review
- High Expression of FAM83B Predicts Poor Prognosis in Patients with Pancreatic Ductal Adenocarcinoma and Correlates with Cell Cycle and Cell Proliferation.Journal of Cancer · 2017Article
- Quercetin and doxorubicin co-encapsulated biotin receptor-targeting nanoparticles for minimizing drug resistance in breast cancer.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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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