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ORIGINAL RESEARCH article
Front. Mol. Biosci.
Sec. Molecular Diagnostics and Therapeutics
Volume 12 - 2025 | doi: 10.3389/fmolb.2025.1548810
This article is part of the Research Topic Exploring and Overcoming Cancer Drug Resistance: Novel Insights and Strategies View all articles
Rapamycin combined with Osimertinib alleviated non-small cell lung cancer by regulating the PARP, Akt/mTOR, and MAPK/ERK signaling pathways
Provisionally accepted- The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
Backgrounds: Non-small cell lung cancer (NSCLC), one kind of common malignant tumor, is accompanied by high morbidity and mortality. The effects and related mechanisms of rapamycin (Rapa) combined with osimertinib (Osi) in treating NSCLC are still unclear. Therefore, this study aims to investigate the effects and related mechanisms of Rapa combined with Osi on NSCLC. Methods: In A549 and PC-9 cells, the Cell Counting Kit-8 (CCK-8) assay was used to select the optimal administrative concentrations of Rapa and Osi and evaluate the cell viability. The Transwell assay and flow cytometry were used to determine the migration, cell cycle, apoptosis, and the level of Reactive Oxygen Species (ROS), respectively. The protein and mRNA expression level of Matrix Metalloproteinase-9 (MMP9), Caspase-3, Microtubule-Associated Protein 1 Light Chain 3 II/I (LC3 II/I), beclin1, Sequestosome 1 (p62), Poly(ADP-ribose) Polymerase (PARP), Mitogen-Activated Protein Kinase (MAPK), Extracellular Signal-Regulated Kinase (ERK), Protein Kinase B (Akt), and Mammalian Target of Rapamycin (mTOR) was determined by Western blot and Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR). Results: The optimal administrative concentrations of Rapa and Osi were 0.5 μM and 1 μM, respectively. Rapamycin combined withOsimertinib significantly decreased the viability of cells, the quantity of migrated cells, the levels of ROS, as well as the mRNA and protein expression levels of MMP9 and p62, Caspase-3, LC3 II/I, beclin1. The combination of the two drugs is markedly more effective than the use of drugs alone.In conclusion, the study demonstrated that Rapamycin combined with Osimertinib can inhibit the cell migration, regulate the cell cycle, promote the autophagy and apoptosis, increase the ROS level and regulate the PARP, MAPK/EKR, and Akt/mTOR pathways in A549 and PC-9 cells, providing a novel theoretical basis for their clinical treatment of NSCLC.
Keywords: rapamycin, Osimertinib, Non-small cell lung cancer, PARP signaling pathway, Akt/mTOR signaling pathway, MAPK/ERK signaling pathway
Received: 20 Dec 2024; Accepted: 12 Feb 2025.
Copyright: © 2025 Ma, Chen and Xiao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Haiping Xiao, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
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