ArticlePloS one2014
The combination of RAD001 and MK-2206 exerts synergistic cytotoxic effects against PTEN mutant gastric cancer cells: involvement of MAPK-dependent autophagic, but not apoptotic cell death pathway.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 53 citations in OpenAlex.
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- Neuron-secreted NLGN3 ameliorates ischemic brain injury via activating Gαi1/3-Akt signaling.Cell death & disease · 2023Article
- Circular RNA 0001789 sponges miR-140-3p and regulates PAK2 to promote the progression of gastric cancer.Journal of translational medicine · 2023Article
- Glypican 1 promotes proliferation and migration in esophagogastric adenocarcinoma via activating AKT/GSK/β-catenin pathway.Journal of gastrointestinal oncology · 2022Article
- The requirement of phosphoenolpyruvate carboxykinase 1 for angiogenesis in vitro and in vivo.Science advances · 2022Article
- LncRNA PINK1-AS promotes Gαi1-driven gastric cancer tumorigenesis by sponging microRNA-200a.Oncogene · 2021Article
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- Neferine treatment enhances the TRAIL‑induced apoptosis of human prostate cancer cells via autophagic flux and the JNK pathway.International journal of oncology · 2020Article
- Molecular mechanisms of synergistic action of Ramucirumab and Paclitaxel in Gastric Cancers cell lines.Scientific reports · 2020Article
- Inhibition of esophageal cancer growth through the suppression of PI3K/AKT/mTOR signaling pathway.OncoTargets and therapy · 2019Article
- The irreversible ERBB1/2/4 inhibitor neratinib interacts with the PARP1 inhibitor niraparib to kill ovarian cancer cells.Cancer biology & therapy · 2018Article
- SC79 protects dopaminergic neurons from oxidative stress.Oncotarget · 2018Article
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- K-Ras mutation and amplification status is predictive of resistance and high basal pAKT is predictive of sensitivity to everolimus in biliary tract cancer cell lines.Molecular oncology · 2017Article
- Ulk1 over-expression in human gastric cancer is correlated with patients' T classification and cancer relapse.Oncotarget · 2017Article
- Curcuminoid EF24 enhances the anti-tumour activity of Akt inhibitor MK-2206 through ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction in gastric cancer.British journal of pharmacology · 2017Article
- Effects of U0126 and MK2206 on cell growth and re-growth of endometriotic stromal cells grown on substrates of varying stiffness.Scientific reports · 2017Article
- CC-223 blocks mTORC1/C2 activation and inhibits human hepatocellular carcinoma cells in vitro and in vivo.PloS one · 2017Article
- Article
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the current study, we showed that the combination of mammalian target of rapamycin (mTOR) inhibitor RAD001 (everolimus) and Akt inhibitor MK-2206 exerted synergistic cytotoxic effects against low-phosphatase and tensin homolog (PTEN) gastric cancer cells (HGC-27 and SNU-601 lines). In HGC-27 cells, RAD001 and MK-2206 synergistically induced G1/S cell cycle arrest, growth inhibition, cell death but not apoptosis. RAD001 and MK-2206 synergistically induced light chain 3B (LC3B) and beclin-1 expression, two important autophagy indicators. Meanwhile, the autophagy inhibitor 3-methyladenine (3-MA) and chloroquine inhibited the cytotoxic effects by RAD001 and MK-2206, suggesting that autophagic, but not apoptotic cell death was important for the cytotoxic effects by the co-administration. We observed that the combination of RAD001 and MK-2206 exerted enhanced effects on Akt/mTOR inhibition, cyclin D1 down-regulation and ERK/MAPK(extracellular signal-regulated kinase/mitogen-activated protein kinases) activation. Intriguingly, MEK/ERK inhibitors PD98059 and U0126 suppressed RAD001 plus MK-2206-induced beclin-1 expression, autophagy induction and cytotoxicity in HGC-27 cells. In conclusion, these results suggested that the synergistic anti-gastric cancer cells ability by RAD001 and MK-2206 involves ERK-dependent autophagic cell death pathway.
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