ArticleCancer biology & therapy2017
The allosteric AKT inhibitor, MK2206, decreases tumor growth and invasion in patient derived xenografts of endometrial cancer.
Article in Cancer biology & therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- A Phase I Study of Dinaciclib in Combination With MK-2206 in Patients With Advanced Pancreatic Cancer.Clinical and translational science · 2020Trial
- A sustained-release depot formulation of β-nicotinamide mononucleotide for alleviating chemotherapy-induced myelosuppression.Materials today. Bio · 2026Article
- Dual PI3K and HDAC inhibitor, CUDC-907, effectively inhibits endometrial cancer growthFrontiers in oncology · 2025Article
- AKT inhibitors in gynecologic oncology: past, present and future.Frontiers in oncology · 2025Review
- Review
- Downregulation of TRIB3 enhances the sensitivity of lung cancer cells to amino acid deprivation by suppressing AKT activation.American journal of cancer research · 2024Article
- Ipatasertib, an oral AKT inhibitor, in combination with carboplatin exhibits anti-proliferative effects in uterine serous carcinoma.Annals of medicine · 2023Article
- Utilizing an Endogenous Progesterone Receptor Reporter Gene for Drug Screening and Mechanistic Study in Endometrial Cancer.Cancers · 2022Article
- Article
- Ad-VT enhances the sensitivity of chemotherapy-resistant lung adenocarcinoma cells to gemcitabine and paclitaxel in vitro and in vivo.Investigational new drugs · 2022Article
- Ipatasertib, an oral AKT inhibitor, inhibits cell proliferation and migration, and induces apoptosis in serous endometrial cancer.American journal of cancer research · 2022Article
- EPHA2 Promotes the Invasion and Migration of Human Tongue Squamous Cell Carcinoma Cal-27 Cells by Enhancing AKT/mTOR Signaling Pathway.BioMed research international · 2021Article
- The AKT inhibitor MK2206 suppresses airway inflammation and the pro‑remodeling pathway in a TDI‑induced asthma mouse model.Molecular medicine reports · 2020Article
- Targeted therapies in gynecological cancers: a comprehensive review of clinical evidence.Signal transduction and targeted therapy · 2020Review
- MK2206 Enhances Cisplatin-Induced Cytotoxicity and Apoptosis in Testicular Cancer Through Akt Signaling Pathway Inhibition.Translational oncology · 2020Article
- DDB1 E3 ligase controls dietary fructose-induced ChREBPα stabilization and liver steatosis via CRY1.Metabolism: clinical and experimental · 2020Article
- Review
- Phosphorylation-Dependent Inhibition of Akt1.Genes · 2018Article
- Patient-Derived Xenograft Models for Endometrial Cancer Research.International journal of molecular sciences · 2018Review
- Apoptin-derived peptide reverses cisplatin resistance in gastric cancer through the PI3K-AKT signaling pathway.Cancer medicine · 2018Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
The purpose of this study was to test the effect of MK2206, an allosteric inhibitor of AKT, on the growth and invasion of patient-derived xenografts (PDX) of endometrial cancer. Three PDX lines, USC1 (uterine serous), EEC2 (endometrioid grade 2) and EEC4 (endometrioid grade 3) of endometrial cancer were grafted under the renal capsule of NSG mice. After 2 weeks of tumor growth the mice were treated with vehicle or 120mg/kg MK2206 twice a week for 3 weeks. Growth of all 3 PDX lines of different type and grade was significantly inhibited in response to MK2206 compared with vehicle control. Histological analysis revealed invasion and spread of EEC2 and EEC4 tumors were significantly decreased with MK2206 treatment. Immunohistochemical analysis showed a decrease in Ki67 in EEC2 upon MK2206 treatment, while USC1 and EEC4 tumors did not show differences in Ki67 levels. PR levels were evident in EEC2 which dramatically increased upon MK2206 treatment. In vitro analysis of EEC4 and AN3CA cells showed a dose-dependent decrease in p(Ser473)-AKT and p(Thr308)-AKT with MK2206. Invasion of EEC4 and AN3CA cells also significantly decreased after 36h and 72h of MK2206 treatment. PDX tumors provide an appropriate model for the testing of compounds that incorporates the heterogeneous nature of endometrial cancer. Further studies to determine efficacy of MK2206 alone or in combination with other compounds can also identify predictors of response to these pathway inhibitors.
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