Objective To explore the effect of autophagic inhibitors chloroquine (CQ) and 3-methyl adenine (3-MA) on apoptosis of non-small cell lung adenocarcinoma NCI-H1975 cells induced by camptothecin (CPT). Methods After NCI-H1975 cells were treated with CPT, cell proliferation was detected by CCK-8 assay, morphological changes of cells were observed by PI staining, and the apoptosis of NCI-H1975 cells was determined by flow cytometry. The levels of autophagy-and apoptosis-related proteins LC3I, LC3II, P62, caspase-3 and poly ADP-ribose polymerase (PARP) and transforming growth factor beta 1 (TGF-beta 1) were detected by Western blot analysis. Results After CPT treatment, the ratio of LC3II to LC3I was raised. The apoptotic protease caspase-3 and substrate PARP were obviously degraded, which could be enhanced by 3-MA but inhibited by CQ. It was also found that the intracellular TGF-beta 1 was reduced after CPT treatment. Conclusion Inhibition of autophagy initiation stage in NCI-H1975 cells can increase the sensitivity of cell apoptosis induced by CPT.
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Bioorg Chem
January 2025
Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, China; College of Science, Yunnan Agricultural University, Kunming 650201, China. Electronic address:
Epidermal growth factor receptor (EGFR) is a starring target for the treatment of non-small cell lung cancer (NSCLC). EGFR tyrosine kinase inhibitors (EGFR-TKIs) have been used to treat NSCLC patients with EGFR-activating mutations. However, most patients invariably develop resistance to these agents due to the occurrence of novel mutations at the EGFR kinase domain.
View Article and Find Full Text PDFMol Divers
December 2024
School of Pharmaceutical Sciences, Guizhou University, Guiyang, 550025, China.
To overcome T790M mutation, a novel series of 4-indazolypyrimidine derivatives were developed as novel EGFR inhibitors employing a scaffold hopping drug design strategy. The biological activities of the target compounds were evaluated against two tumor cell lines (A431 and NCI-H1975), normal cell 2BS and EGFR kinase. The results indicated that the majority of the compounds exhibited promising antitumor activity and low toxicity.
View Article and Find Full Text PDFIn Vivo
October 2024
Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (Cinvestav-IPN), Ciudad de México, México;
Sci Rep
October 2024
Collaborative Innovation Center for Antitumor Active Substance Research and Development, Institute of Biochemistry and Molecular Biology, Guangdong Medical University, Zhanjiang, 524023, People's Republic of China.
In our previous study, we have isolated cytochalasin H (CyH) from endophytic fungus derived from mangrove plant and found that CyH inhibited the proliferation of non-small cell lung cancer (NSCLC) cells. Recently, epidermal growth factor receptor (EGFR) activation and programmed cell death 1 ligand (PD-L1) expression have been demonstrated to mediate NSCLC resistance to gefitinib, first-generation EGFR tyrosine kinase inhibitor (EGFR-TKI). Here, we further investigated the effect of CyH on EGFR activation, PD-L1 expression, and gefitinib sensitivity in NSCLC cell lines, A549 (wild-type EGFR), HCC827 (EGFR mutation), and NCI-H1975 (dual EGFR mutations and acquired gefitinib resistance) and animal model.
View Article and Find Full Text PDFJ Cancer Res Clin Oncol
October 2024
Department of Clinical Sciences Lund, Division of Pathology, Lund University, BMC B13, Klinikgatan 26, Lund, SE-221 00, Sweden.
Purpose: The aim of this study was to set up reliable and reproducible culture conditions for 3D tumoroids derived from non-small cell lung cancer (NSCLC) cell lines to enable greater opportunity for successful cultivation of patient-derived samples.
Methods: Four NSCLC cell lines, two adenocarcinomas (A549, NCI-H1975) and two squamous cell carcinomas (HCC-95, HCC-1588), were first cultured in traditional 2D settings. Their expected expression profiles concerning TTF-1, CK7, CK5, and p40 status were confirmed by immunohistochemistry (IHC) before the generation of 3D cultures.
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