ArticlePloS one2015
Rapamycin Enhances the Anti-Cancer Effect of Dasatinib by Suppressing Src/PI3K/mTOR Pathway in NSCLC Cells.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 43 citations in OpenAlex.
- Dual molecular therapy targeting tumor cell heterogeneity improves therapeutic efficacy in glioblastoma.iScience · 2025Article
- Current and future of targeted therapies against BCR::ABL kinases.Journal of the Egyptian National Cancer Institute · 2025Review
- Rapamycin combined with osimertinib alleviated non-small cell lung cancer by regulating the PARP, Akt/mTOR, and MAPK/ERK signaling pathways.Frontiers in molecular biosciences · 2025Article
- Dasatinib induces apoptosis and autophagy by suppressing the PI3K/Akt/mTOR pathway in bladder cancer cells.Investigative and clinical urology · 2024Article
- A kinome drug screen identifies multi-TKI synergies and ERBB2 signaling as a therapeutic vulnerability in MYC/TYR subgroup atypical teratoid rhabdoid tumors.Neuro-oncology · 2024Article
- AKT-independent signaling in PIK3CA-mutant thyroid cancer mediates resistance to dual SRC and MEK1/2 inhibition.Medical oncology (Northwood, London, England) · 2023Article
- Dasatinib-induced spleen contraction leads to transient lymphocytosis.Blood advances · 2023Article
- Article
- PEDF inhibits non‑small cell lung cancer proliferation by suppressing autophagy through downregulation of AMPK‑ULK1 signaling.Oncology reports · 2022Article
- Dasatinib enhances curcumin-induced cytotoxicity, apoptosis and protective autophagy in human schwannoma cells HEI-193: The role of Akt/mTOR/p70S6K signalling pathway.Acta pharmaceutica (Zagreb, Croatia) · 2022Article
- Anti-aging: senolytics or gerostatics (unconventional view).Oncotarget · 2021Review
- A lncRNA TCL6-miR-155 Interaction Regulates the Src-Akt-EMT Network to Mediate Kidney Cancer Progression and Metastasis.Cancer research · 2021Observational
- Agrin Promotes Non-Small Cell Lung Cancer Progression and Stimulates Regulatory T CellsFrontiers in oncology · 2021Article
- Src Family Kinase Inhibitors Block Translation of Alphavirus Subgenomic mRNAs.Antimicrobial agents and chemotherapy · 2019Article
- Investigational multitargeted kinase inhibitors in development for head and neck neoplasms.Expert opinion on investigational drugs · 2019Review
- Targeting mTOR and Src restricts hepatocellular carcinoma growth in a novel murine liver cancer model.PloS one · 2019Article
- EPH receptor signaling as a novel therapeutic target in NF2-deficient meningioma.Neuro-oncology · 2018Article
- Combined inhibition of PI3K and Src kinases demonstrates synergistic therapeutic efficacy in clear-cell renal carcinoma.Oncotarget · 2018Article
- Adaptive metabolic rewiring to chronic SFK inhibition.Oncotarget · 2017Article
- A Pan-Cancer Proteogenomic Atlas of PI3K/AKT/mTOR Pathway Alterations.Cancer cell · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Src and the mammalian target of rapamycin (mTOR) signaling are commonly activated in non-small cell lung cancer (NSCLC) and hence potential targets for chemotherapy. Although the combined use of Src inhibitor Dasatinib with other chemotherapeutic agents has shown superior efficacy for cancer treatment, the mechanisms that lead to enhanced sensitivity of Dasatinib are not completely understood. In this study, we found that Rapamycin dramatically enhanced Dasatinib-induced cell growth inhibition and cell cycle G1 arrest in human lung adenocarcinoma A549 cells without affecting apoptosis. The synergistic effects were consistently correlated with the up-regulation of cyclin-dependent kinases inhibitor proteins, including p16, p19, p21, and p27, as well as the repression of Cdk4 expression and nuclear translocation. Mechanistic investigations demonstrated that FoxO1/FoxO3a and p70S6K/4E-BP1, the molecules at downstream of Src-PI3K-Akt and mTOR signaling, were significantly suppressed by the combined use of Dasatinib and Rapamycin. Restraining Src and mTOR with small interfering RNA in A549 cells further confirmed that the Src/PI3K/mTOR Pathway played a crucial role in enhancing the anticancer effect of Dasatinib. In addition, this finding was also validated by a series of assays using another two NSCLC cell lines, NCI-H1706 and NCI-H460. Conclusively, our results suggested that the combinatory application of Src and mTOR inhibitors might be a promising therapeutic strategy for NSCLC treatment.
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