Rapamycin combined with osimertinib alleviated non-small cell lung cancer by regulating the PARP, Akt/mTOR, and MAPK/ERK signaling pathways.

IF 3.9 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Frontiers in Molecular Biosciences Pub Date : 2025-03-07 eCollection Date: 2025-01-01 DOI:10.3389/fmolb.2025.1548810

Qingrong Ma, Kai Chen, Haiping Xiao

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引用次数: 0

Abstract

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 with Osimertinib 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.

Conclusion: 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.

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来源期刊

Frontiers in Molecular Biosciences Biochemistry, Genetics and Molecular Biology-Biochemistry

CiteScore

7.20

自引率

4.00%

发文量

1361

审稿时长

14 weeks

期刊介绍： Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology. Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life. In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.