ArticleCancer cell international2015
Inhibition of the AKT pathway in cholangiocarcinoma by MK2206 reduces cellular viability via induction of apoptosis.
Article in Cancer cell international, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 32 citations in OpenAlex.
- Review
- Dual Inhibition of PI3 Kinase and MAP Kinase Signaling Pathways in Intrahepatic Cholangiocellular Carcinoma Cell Lines Leads to Proliferation Arrest but Not Apoptosis.Current issues in molecular biology · 2024Article
- Therapeutic Implications of Ceritinib in Cholangiocarcinoma beyond ALK Expression and Mutation.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Article
- Development of Possible Next Line of Systemic Therapies for Gemcitabine-Resistant Biliary Tract Cancers: A Perspective from Clinical Trials.Biomolecules · 2021Review
- Promising Molecular Targets for the Targeted Therapy of Biliary Tract Cancers: An Overview.OncoTargets and therapy · 2021Review
- Review
- Downregulation of ABCA1 and ABCG1 transporters by simvastatin in cholangiocarcinoma cells.Oncology letters · 2019Article
- High Survivin and Low Zinc Finger of the Cerebellum 1 Expression Indicates Poor Prognosis in Triple-negative Breast Carcinoma.Journal of breast cancer · 2019Article
- ZIC1 acts a tumor suppressor in breast cancer by targeting survivin.International journal of oncology · 2018Article
- RACK1 Silencing Induces Cell Apoptosis and Inhibits Cell Proliferation in Hepatocellular Carcinoma MHCC97-H Cells.Pathology oncology research : POR · 2018Article
- The potential role of comprehensive genomic profiling to guide targeted therapy for patients with biliary cancer.Therapeutic advances in gastroenterology · 2017Review
- Signaling pathways as therapeutic targets in biliary tract cancer.Expert opinion on therapeutic targets · 2017Review
- Analysis of PI3K pathway components in human cancers.Oncology letters · 2016Article
- Prediction of Angiopoietin-like Protein 4-related Signaling Pathways in Cholangiocarcinoma Cells.Cancer genomics & proteomicsArticle
- Flavokawain B Inhibits Growth of Cholangiocarcinoma Cells by Suppressing the Akt Pathway.In vivo (Athens, Greece)Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionCholangiocarcinoma (CCA) is an aggressive disease with limited effective treatment options. The PI3K/Akt/mTOR pathway represents an attractive therapeutic target due to its frequent dysregulation in CCA. MK2206, an allosteric Akt inhibitor, has been shown to reduce cellular proliferation in other cancers. We hypothesized that MK2206 mediated inhibition of Akt would impact CCA cellular viability. STUDY
methodsPost treatment with MK2206 (0-2 μM), cellular viability was assessed in two human CCA cell lines-CCLP-1 and SG231-using an MTT assay. Lysates from the MK2206 treated CCA cells were then examined for apoptotic marker expression levels using Western blot analysis. Additionally, the effect on cellular proliferation of MK2206 treatment on survivin depleted cells was determined.
resultsCCLP-1 and SG231 viability was significantly reduced at MK2206 concentrations of 0.5, 1, and 2 μM by approximately 44%, 53%, and 64% (CCLP-1; p = 0.01) and 32%, 32%, and 42% (SG231; p < 0.00005) respectively. Western analysis revealed a decrease in AKT(Ser473), while AKT(Thr308) expression was unchanged. In addition, cleaved PARP as well as survivin expression increased while pro-caspase 3 and 9 levels decreased with treatment. Depletion of survivin in CCLP-1 cells resulted in apoptosis as evidenced by increased cleaved PARP. In addition, survivin siRNA further enhanced the antitumor activity of MK2206.
conclusionsThis study demonstrates that by blocking phosphorylation of Akt at serine473, CCA cellular growth is reduced. The growth suppression appears to be mediated via apoptosis. Importantly, combination of survivin siRNA transfection and MK2206 treatment significantly decreased cell viability.
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