03 August 2017 : Laboratory Research
Synergistic Effect of Notch-3-Specific Inhibition and Paclitaxel in Non-Small Cell Lung Cancer (NSCLC) Cells Via Activation of The Intrinsic Apoptosis PathwayFenglian He1ADG, Ting Du1BC, Qian Jiang1F, Yanbei Zhang1E*
Med Sci Monit 2017; 23:3760-3769
BACKGROUND: Lung cancers are resistant to conventional chemotherapeutic interventions such as paclitaxel. Notch signaling is crucial in the chemoresistance of lung cancer cells. The Notch inhibitor gamma-secretase inhibitor (GSI) inhibits the Notch signaling pathway.
MATERIAL AND METHODS: Here, we evaluated how Notch-3 inhibition by GSI can enhance the sensitivity of lung cancer cells to paclitaxel. To study how Notch-3-specific inhibition affects non-small cell lung cancer (NSCLC), we compared the cell viability, apoptosis, and colony formation of A549 and H1299 cells treated with Notch-3 siRNA and GSI.
RESULTS: The expression levels of Notch-3 or Notch intracellular domain 3 (NICD3) and apoptosis-related proteins were measured and compared between different groups. Notch-3 was significantly overexpressed in both cell lines, and Notch-3 expression was elevated after paclitaxel treatment, indicating activation of the Notch signaling pathway. Inhibition of the Notch signaling pathway by GSI and Notch-3 siRNA reduced cell proliferation and induced apoptosis in A549 and H1299 cells, thereby boosting sensitivity of the cell lines to paclitaxel. Concomitant treatment with paclitaxel and GSI or siRNA downregulated Bcl-2 expression and upregulated Bax expression levels.
CONCLUSIONS: These results indicate a synergistic effect of Notch-3-specific inhibition and paclitaxel through alteration of the intrinsic apoptosis pathway, which was involved in Notch-3-induced chemoresistance in NSCLC cells, and GSI inhibited Notch-3-induced chemoresistance in a concentration-dependent manner. This approach that combines Notch-3-specific inhibition and paclitaxel would be likely to apply in NSCLC.
Keywords: Amyloid Precursor Protein Secretases, paclitaxel, Receptors, Notch, RNA, Small Interfering
01 March 2024 : EditorialEditorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and Transfusion-Dependent β-Thalassemia
Med Sci Monit 2024; 30:e944204
15 Jan 2024 : Clinical ResearchComparison of Modified Shock Index and Shock Index for Predicting Massive Transfusion in Women with Primary...
Med Sci Monit In Press; DOI: 10.12659/MSM.943286
15 Jan 2024 : Database AnalysisBibliometric Analysis of Brain Stimulation Technologies in Sleep Disorders
Med Sci Monit In Press; DOI: 10.12659/MSM.942687
15 Jan 2024 : Clinical ResearchClinical Outcomes of Arthroscopic Surgery in Patients with Gluteal Muscle Contracture: Single-Institution R...
Med Sci Monit In Press; DOI: 10.12659/MSM.942945
Most Viewed Current Articles
16 May 2023 : Clinical ResearchElectrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...
Med Sci Monit 2023; 29:e940387
17 Jan 2024 : Review articleVaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron Variant
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical ResearchPrevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase Levels
Med Sci Monit 2022; 28:e937990