Epidermal growth factor receptor (EGFR) L858R/T790 M mutation-mediated gefitinib resistance (GR) is a frequent dilemma in the treatment of non-small cell lung cancer (NSCLC). This study aimed to explore the effect of jatrorrhizine on treating GR NSCLC and its possible mechanism of action. Cell viability, migration, invasion, and apoptosis detection were used to study the effect of jatrorrhizine on suppressing H1975 cells. Swiss Target Prediction and Traditional Chinese Medicine Database, GeneCards, and Online Mendelian Inheritance in Man databases and molecular docking were carried out to explore the targets of jatrorrhizine. Western blot was conducted to detect the effect of jatrorrhizine on inhibiting the PI3K/mTOR signaling pathway. Jatrorrhizine has a similar anti-tumor effect on inhibiting the proliferation and migration of H1975 cells. Jatrorrhizine could dose-dependently inhibit the proliferation, and invasion and promote the apoptosis of human NSCLC cells. The PI3K-Akt signaling pathway was preliminarily predicted (Kyoto Encyclopedia of Genes and Genomes) and verified (Molecular docking) to be a critical pathway of jatrorrhizine against NSCLC. The cytotoxic assay of PI3K/mTOR inhibitor PKI-402 on H1975 cells and ADP-Glo Kinase assay of the inhibitory effect of jatrorrhizine on PI3K kinase activity. Western blot verified that jatrorrhizine down-regulates the phosphorylation of PI3K/mTOR in H1975 cells. Our results revealed that jatrorrhizine is a potentially novel compound that inhibits GR NSCLC by inhibiting PI3K/mTOR phosphorylation.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/cbdv.202402598 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Induction of Senescence in Lung Cancer Cells by Qidongning Formula via the Transcription Factor EGR1.
Integr Cancer Ther
March 2025
Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
The purpose of this study was to investigate the role of the early growth response gene 1 (EGR1) in inducing senescence in lung cancer cells by Qidongning Formula (QDF). Cell-Counting-Kit-8 was used to study the effect of QDF on A549 and NCI-H1975 cells proliferation. Senescence-associated β-galactosidase (SA-β-GAL) staining was used to examine the effect of QDF on cellular senescence.
View Article and Find Full Text PDFSecretomes From Non-Small Cell Lung Cancer Cells Induce Endothelial Plasticity Through a Partial Endothelial-to-Mesenchymal Transition.
Cancer Med
March 2025
Univ Angers, Inserm, CNRS, MINT, SFR ICAT, Angers, France.
Aim: The tumor microenvironment (TME) of non-small cell lung cancer (NSCLC) is highly heterogeneous and is involved in tumorigenesis and resistance to therapy. Among the cells of the TME, endothelial cells are associated with the latter processes through endothelial-to-mesenchymal transition (EndMT). During EndMT, endothelial cells (ECs) progressively lose their endothelial phenotype in favor of a mesenchymal phenotype, which favors the production of cancer-associated fibroblasts (CAFs).
View Article and Find Full Text PDFStructure-Based Design of New LSD1/EGFR Dual Inhibitors for Treating EGFR Mutant NSCLC Cancers.
J Med Chem
February 2025
College of Chemistry, Pingyuan Laboratory, Zhengzhou University, Zhengzhou 450001, China.
Epigenetic changes, such as LSD1 dysregulation, contribute to acquired resistance in EGFR mutant NSCLCs and reduce the effectiveness of current therapeutics. To address the challenges, we herein reported the structure-based design of new LSD1/EGFR dual inhibitors, of which represents the shortlisted lead compound with high potency, selectivity, and unique dual modes of action (namely irreversibly binding to EGFR but reversibly binding to LSD1). effectively inhibited growth in both parent- and TKI-resistant NSCLC cells.
View Article and Find Full Text PDFGeniposide Inhibits Non-Small Cell Lung Cancer by Regulating Proliferation, Apoptosis, Invasion, Migration, Epithelial-Mesenchymal Transition, and Cancer Stem-Like Cell Property Via Wnt/β-Catenin Pathway.
Biochem Genet
February 2025
School of Mathematics and Physics, Nanyang Institute of Technology, Nanyang, 473004, China.
Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. Geniposide, an active compound of Gardeniae Fructus, has antithrombotic, antitumor, neuroprotective, hepatoprotective, cholestatic, and other effects. The present study aimed to investigate the effects of geniposide on NSCLC cells, as well as its underlying mechanism.
View Article and Find Full Text PDFAnlotinib enhances the anti-tumor activity of osimertinib in patients with non-small cell lung cancer by reversing drug resistance.
Transl Lung Cancer Res
January 2025
Department of Respiratory and Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Background: Osimertinib, a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), significantly improves the prognosis of patients with -mutant non-small cell lung cancer (NSCLC). However, subsequently-acquired resistance limits its effectiveness. This study aimed to explore the efficacy of anlotinib, a multitarget inhibitor of angiogenesis, in combination with osimertinib using and EGFR-TKI-sensitive and EGFR-TKI-resistant models.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!