Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

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 Pathway

Fenglian He1ADG, Ting Du1BC, Qian Jiang1F, Yanbei Zhang1E*

DOI: 10.12659/MSM.902641

Med Sci Monit 2017; 23:3760-3769

Abstract

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

Add Comment 0 Comments

Editorial

01 July 2024 : Editorial  

Editorial: The Global Threats of Increasing Antimicrobial Resistance Require New Approaches to Drug Development, Including Molecular Antimicrobial Adjuvants

Dinah V. Parums

DOI: 10.12659/MSM.945583

Med Sci Monit 2024; 30:e945583

0:00

In Press

Clinical Research  

Assessment of Digital Dentistry Knowledge and Practices Among Dental Students at King Faisal University, Sa...

Med Sci Monit In Press; DOI: 10.12659/MSM.944692  

0:00

Database Analysis  

Local Government Initiatives: A Comprehensive Analysis of Infertility Diagnostic and Treatment Programs in ...

Med Sci Monit In Press; DOI: 10.12659/MSM.943976  

0:00

Clinical Research  

Gender-Specific Risk Factors for Asymmetric Bone Density in Adult Degenerative Lumbar Scoliosis: A Retrospe...

Med Sci Monit In Press; DOI: 10.12659/MSM.944137  

Review article  

Innovative Approaches to Enhance and Measure Medication Adherence in Chronic Disease Management: A Review

Med Sci Monit In Press; DOI: 10.12659/MSM.944605  

Most Viewed Current Articles

17 Jan 2024 : Review article   3,672,994

Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron Variant

DOI :10.12659/MSM.942799

Med Sci Monit 2024; 30:e942799

0:00

14 Dec 2022 : Clinical Research   1,585,207

Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase Levels

DOI :10.12659/MSM.937990

Med Sci Monit 2022; 28:e937990

0:00

16 May 2023 : Clinical Research   690,865

Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...

DOI :10.12659/MSM.940387

Med Sci Monit 2023; 29:e940387

0:00

01 Jan 2022 : Editorial   50,699

Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...

DOI :10.12659/MSM.935952

Med Sci Monit 2022; 28:e935952

0:00

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750