ArticleCancer biology & therapy2013
Inhibition of oncogenic Pim-3 kinase modulates transformed growth and chemosensitizes pancreatic cancer cells to gemcitabine.
Article in Cancer biology & therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Identification and Validation of an Inhibitor of the Protein Kinases PIM and DYRK.Journal of medicinal chemistry · 2026Article
- AUM-302, a novel triple PIM/PI3K/mTOR inhibitor, synergizes with RAS inhibition and impedes the growth of pancreatic ductal adenocarcinoma spheroids and organoids.Frontiers in pharmacology · 2026Article
- A Promising Druggable Target for Translational Therapy of Ovarian Cancer: A Molecular Profiling of Therapeutic Innovations, Extracellular Vesicle Acquired Resistance, and Signaling Pathways.Current medicinal chemistry · 2025Review
- PIM1 kinase and its diverse substrate in solid tumors.Cell communication and signaling : CCS · 2024Review
- PIM3 Kinase: A Promising Novel Target in Solid Cancers.Cancers · 2024Review
- AUM302, a novel triple kinase PIM/PI3K/mTOR inhibitor, is a potent in vitro pancreatic cancer growth inhibitor.PloS one · 2023Article
- The Role of PIM Kinases in Pediatric Solid Tumors.Cancers · 2022Review
- PIM kinases mediate resistance to cisplatin chemotherapy in hepatoblastoma.Scientific reports · 2021Article
- AZD1208, a Pan-Pim Kinase Inhibitor, Has Anti-Growth Effect on 93T449 Human Liposarcoma Cells via Control of the Expression and Phosphorylation of Pim-3, mTOR, 4EBP-1, S6, STAT-3 and AMPK.International journal of molecular sciences · 2019Article
- Phase I studies of AZD1208, a proviral integration Moloney virus kinase inhibitor in solid and haematological cancers.British journal of cancer · 2018Article
- Pim-3 enhances melanoma cell migration and invasion by promoting STAT3 phosphorylation.Cancer biology & therapy · 2018Article
- Ubenimex suppresses Pim-3 kinase expression by targeting CD13 to reverse MDR in HCC cells.Oncotarget · 2017Article
- Pim-3 Regulates Stemness of Pancreatic Cancer Cells via Activating STAT3 Signaling Pathway.Journal of Cancer · 2017Article
- Pim-3 is a Critical Risk Factor in Development and Prognosis of Prostate Cancer.Medical science monitor : international medical journal of experimental and clinical research · 2016Article
- MiR-377 inhibits the proliferation of pancreatic cancer by targeting Pim-3.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- PIM-1 contributes to the malignancy of pancreatic cancer and displays diagnostic and prognostic value.Journal of experimental & clinical cancer research : CR · 2016Article
- MYC in pancreatic cancer: novel mechanistic insights and their translation into therapeutic strategies.Oncogene · 2016Review
- MicroRNA-33a-mediated downregulation of Pim-3 kinase expression renders human pancreatic cancer cells sensitivity to gemcitabine.Oncotarget · 2015Article
- Pathophysiological roles of Pim-3 kinase in pancreatic cancer development and progression.World journal of gastroenterology · 2014Review
- DNA microarray reveals ZNF195 and SBF1 are potential biomarkers for gemcitabine sensitivity in head and neck squamous cell carcinoma cell lines.International journal of clinical and experimental pathology · 2014Article
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Authors and funding
11 authors at 7 institutions in 3 countries.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a 5-year survival rate of only 6%. Although the cytosine analog gemcitabine is the drug commonly used to treat PDAC, chemoresistance unfortunately renders the drug ineffective. Thus, strategies that can decrease this resistance will be essential for improving the dismal outcome of patients suffering from this disease. We previously observed that oncogenic Pim-1 kinase was aberrantly expressed in PDAC tissues and cell lines and was responsible for radioresistance. Furthermore, members of the Pim family have been shown to reduce the efficacy of chemotherapeutic drugs in cancer. Therefore, we attempted to evaluate the role of Pim-3 in chemoresistance of PDAC cells. We were able to confirm upregulation of the Pim-3 oncogene in PDAC tissues and cell lines versus normal samples. Biological consequences of inhibiting Pim-3 expression with shRNA-mediated suppression included decreases in anchorage-dependent growth, invasion through Matrigel and chemoresistance to gemcitabine as measured by caspase-3 activity. Additionally, we were able to demonstrate that Pim-1 and Pim-3 play overlapping but non-identical roles as it relates to gemcitabine sensitivity of pancreatic cancer cells. To further support the role of Pim-3 suppression in sensitizing PDAC cells to gemcitabine, we used the pharmacological Pim kinase inhibitor SGI-1776. Treatment of PDAC cells with SGI-1776 resulted in decreased phosphorylation of the proapoptotic protein Bad and cell cycle changes. When SGI-1776 was combined with gemcitabine, there was a greater decrease in cell viability in the PDAC cells versus cells treated with either of the drugs separately. These results suggest combining drug therapies that inhibit Pim kinases, such as Pim-3, with chemotherapeutic agents, to aid in decreasing chemoresistance in pancreatic cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.