ArticleCells2021
Suppression of PI3K/Akt/mTOR/c-Myc/mtp53 Positive Feedback Loop Induces Cell Cycle Arrest by Dual PI3K/mTOR Inhibitor PQR309 in Endometrial Cancer Cell Lines.
Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 47 citations in OpenAlex.
- Integrated multi-omics and machine learning highlight PTM-related genes as potential biomarkers in endometrial cancer.Translational oncology · 2026Article
- Regulation of autophagy by the p53 family and the implications for cancer therapies.Discover oncology · 2026Review
- Oxidative stress as a nexus: Integrating mitophagy and ferroptosis in endometrial carcinogenesis (Review).Oncology letters · 2026Review
- PI3K/AKT/mTOR pathway and c-Myc inhibit hepatocyte suspension under simulated microgravity.NPJ microgravity · 2025Article
- Leiomodin 1 haploinsufficiency promotes smooth muscle cell proliferation and increases neointimal lesion size.Vascular pharmacology · 2025Article
- Therapeutic and Prognostic Relevance of Cancer Stem Cell Populations in Endometrial Cancer: A Narrative Review.Diagnostics (Basel, Switzerland) · 2025Review
- Exploring the active ingredients of Banzhilian and its mechanism of action on diabetic Gastric cancer based on network pharmacology.Scientific reports · 2025Article
- Silencing PPP2R1A inhibits the progression of gastric cancer cells.Journal of cancer research and clinical oncology · 2025Article
- The Importance of Cancer Stem Cells and Their Pathways in Endometrial Cancer: A Narrative Review.Cells · 2025Review
- Targeted inhibition of integrin αVβ3 induces cytotoxicity and suppresses migration ability in ovarian cancer cells and tumor spheroids.International journal of medical sciences · 2025Article
- The activity of pyrazoline B compound in inhibiting proliferation of breast cancer cells with human epidermal growth factor receptor 2 overexpression.Contemporary oncology (Poznan, Poland) · 2025Article
- Phosphocholine inhibits proliferation and reduces stemness of endometrial cancer cells by downregulating mTOR-c-Myc signaling.Cellular and molecular life sciences : CMLS · 2024Article
- Cannabidiol suppresses proliferation and induces cell death, autophagy and senescence in human cholangiocarcinoma cells via the PI3K/AKT/mTOR pathway.Journal of traditional and complementary medicine · 2024Article
- The resistance to anoikis, mediated by Spp1, and the evasion of immune surveillance facilitate the invasion and metastasis of hepatocellular carcinoma.Apoptosis : an international journal on programmed cell death · 2024Article
- Small molecule targeted therapies for endometrial cancer: progress, challenges, and opportunities.RSC medicinal chemistry · 2024Review
- Development, synthesis and validation of improved c-Myc/Max inhibitors.Journal of cellular and molecular medicine · 2024Article
- PQR309, a dual PI3K/mTOR inhibitor, synergizes with gemcitabine by impairing the GSK-3β and STAT3/HSP60 signaling pathways to treat nasopharyngeal carcinoma.Cell death & disease · 2024Article
- JMJD3 regulate H3K27me3 modification via interacting directly with TET1 to affect spermatogonia self-renewal and proliferation.BMC genomics · 2024Article
- Protective Effect and Related Mechanism of Modified Danggui Buxue Decoction on Retinal Oxidative Damage in Mice based on Network Pharmacology.Current pharmaceutical design · 2024Article
- Targeted Inhibition of the PI3K/Akt/mTOR Signaling Axis: Potential for Sarcoma Therapy.Mini reviews in medicinal chemistry · 2024Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Gene mutations in PIK3CA, PIK3R1, KRAS, PTEN, and PPP2R1A commonly detected in type I endometrial cancer lead to PI3K/Akt/mTOR pathway activation. Bimiralisib (PQR309), an orally bioavailable selective dual inhibitor of PI3K and mTOR, has been studied in preclinical models and clinical trials. The aim of this study is to evaluate the anticancer effect of PQR309 on endometrial cancer cells. PQR309 decreased cell viability in two-dimensional and three-dimensional cell culture models. PQR309 induced G1 cell cycle arrest and little cell death in endometrial cancer cell lines. It decreased CDK6 expression and increased p27 expression. Using the Proteome Profiler Human XL Oncology Array and Western blot assay, the dual inhibitor could inhibit the expressions of c-Myc and mtp53. KJ-Pyr-9, a c-Myc inhibitor, was used to prove the role of c-Myc in endometrial cancer survival and regulating the expression of mtp53. Knockdown of mtp53 lowered cell proliferation, Akt/mTOR pathway activity, and the expressions of c-Myc. mtp53 silence enhanced PQR309-inhibited cell viability, spheroid formation, and the expressions of p-Akt, c-Myc, and CDK6. This is the first study to reveal the novel finding of the PI3K/mTOR dual inhibitor in lowering cell viability by abolishing the PI3K/Akt/mTOR/c-Myc/mtp53 positive feedback loop in endometrial cancer cell lines.
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Registered trials
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 Socratic graph.