ArticleCancer research and treatment2019
Pan-Pim Kinase Inhibitor AZD1208 Suppresses Tumor Growth and Synergistically Interacts with Akt Inhibition in Gastric Cancer Cells.
Article in Cancer research and treatment, 2019. 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, 22 citations in OpenAlex.
- Berberine impedes the DNA damage repair to inhibit colorectal cancer by regulating the SOX17/TCF4/PIM3 axis.Molecular genetics and genomics : MGG · 2026Article
- DamageZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Article
- Unraveling the role of host kinase PIM1 in Toxoplasma gondii infection: Implications for therapies.PLoS neglected tropical diseases · 2026Article
- In Silico Identification of Lepiotaprocerin C as a Promising PIM-1 Kinase Inhibitor: An Integrated Docking, Molecular Dynamics, MM/PBSA, QSAR, and ADMET Study.Bioinformatics and biology insights · 2026Article
- Combining PIM-2 and PARP1 Inhibitors Induces MICA Expression on Multiple Myeloma Cells to Activate NK Cells through NKG2D Binding.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Prognostic Model Construction of Disulfidptosis-Related Genes and Targeted Anticancer Drug Research in Pancreatic Cancer.Molecular biotechnology · 2025Article
- A literature review of recent advances in gastric cancer treatment: exploring the cross-talk between targeted therapies.Cancer cell international · 2025Review
- PIM1 kinase and its diverse substrate in solid tumors.Cell communication and signaling : CCS · 2024Review
- The evaluation of six genes combined value in glioma diagnosis and prognosis.Journal of cancer research and clinical oncology · 2023Article
- Antitumor effect of a WEE1 inhibitor and potentiation of olaparib sensitivity by DNA damage response modulation in triple-negative breast cancer.Scientific reports · 2020Article
- Inhibition of PIM1 attenuates the stem cell-like traits of breast cancer cells by promoting RUNX3 nuclear retention.Journal of cellular and molecular medicine · 2020Article
- TDP1 and TOP1 Modulation in Olaparib-Resistant Cancer Determines the Efficacy of Subsequent Chemotherapy.Cancers · 2020Article
- Pim-1 inhibitor SMI-4a suppresses tumor growth in non-small cell lung cancer via PI3K/AKT/mTOR pathway.OncoTargets and therapy · 2019Article
- Review
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
purposePim kinases are highly conserved serine/threonine kinases, and different expression patterns of each isoform (Pim-1, Pim-2, and Pim-3) have been observed in various types of human cancers, including gastric cancer. AZD1208 is a potent and selective inhibitor that affects all three isoforms of Pim. We investigated the effects of AZD1208 as a single agent and in combination with an Akt inhibitor in gastric cancer cells. MATERIALS AND
methodsThe antitumor activity of AZD1208 with/without an Akt inhibitor was evaluated in a large panel of gastric cancer cell lines through growth inhibition assays. The underlying mechanism was also examined by western blotting, immunofluorescence assay, and cell cycle analysis.
resultsAZD1208 treatment decreased gastric cancer cell proliferation rates and induced autophagy only in long-term culture systems. Light chain 3B (LC3B), a marker of autophagy, was increased in sensitive cells in a dose-dependent manner with AZD1208 treatment, which suggested that the growth inhibition effect of AZD1208 was achieved through autophagy, not apoptosis. Moreover, we found that cells damaged by Pim inhibition were repaired by activation of the DNA damage repair pathway, which promoted cell survival and led the cells to become resistant to AZD1208. We also confirmed that the combination of an Akt inhibitor with AZD1208 produced a highly synergistic effect in gastric cancer cell lines.
conclusionTreatment with AZD1208 alone induced considerable cell death through autophagy in gastric cancer cells. Moreover, the combination of AZD1208 with an Akt inhibitor showed synergistic antitumor effects through regulation of the DNA damage repair pathway.
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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.