Logo Medical Science Monitor

Call: +1.631.470.9640
Closed: National Holiday

Contact Us

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

15 May 2018 : Laboratory Research  

Study on the Mechanism of Cell Cycle Checkpoint Kinase 2 (CHEK2) Gene Dysfunction in Chemotherapeutic Drug Resistance of Triple Negative Breast Cancer Cells

Li Luo12ABCDEFG, Wei Gao3ABCDEFG, Jinghui Wang1BCDE, Dingxue Wang1BCD, Xiaobo Peng4CD, Zhaoyang Jia5CD, Ye Jiang2DE, Gongzhuo Li2EF, Dongxin Tang6ABCDEFG*, Yajie Wang4ABCDEFG

DOI: 10.12659/MSM.907256

Med Sci Monit 2018; 24: LBR3176-3183

Abstract

BACKGROUND: This study aimed to investigate the mechanism of CHEK2 gene dysfunction in drug resistance of triple negative breast cancer (TNBC) cells.

MATERIAL AND METHODS: To perform our study, a stable CHEK2 wild type (CHEK2 WT) or CHEK2 Y390C mutation (CHEK2 Y390C) expressed MDA-MB-231 cell line was established. MTT assay, cell apoptosis assay and cell cycle assay were carried out to analyze the cell viability, apoptosis, and cell cycle respectively. Western blotting and qRT-PCR were applied for related protein and gene expression detection.

RESULTS: We found that the IC50 value of DDP (Cisplatin) to CHEK2 Y390C expressed MDA-MB-231 cells was significantly higher than that of the CHEK2 WT expressed cells and the control cells. After treatment with DDP for 48 h, cells expressing CHEK2 WT showed lower cell viability than that of the CHEK2 Y390C expressed cells and the control cells; compared with the CHEK2 Y390C expressed cells and the control cells, cells expressing CHEK2 WT showed significant G1/S arrest. Meanwhile, we found that compared with the CHEK2 Y390C expressed cells and the control cells, cell apoptosis was significantly increased in CHEK2 WT expressed cells. Moreover, our results suggested that cells expressing CHEK2 WT showed higher level of p-CDC25A, p-p53, p21, Bax, PUMA, and Noxa than that of the CHEK2 Y390C expressed cells and the control cells.

CONCLUSIONS: Our findings indicated that CHEK2 Y390C mutation induced the drug resistance of TNBC cells to chemotherapeutic drugs through administrating cell apoptosis and cell cycle arrest via regulating p53 activation and CHEK2-p53 apoptosis pathway.

Keywords: Checkpoint Kinase 2, Drug Resistance, Triple Negative Breast Neoplasms

Add Comment 0 Comments

Editorial

01 May 2024 : Editorial  

Editorial: First Regulatory Approval for Adoptive Cell Therapy with Autologous Tumor-Infiltrating Lymphocytes (TILs) – Lifileucel (Amtagvi)

Dinah V. Parums

DOI: 10.12659/MSM.944927

Med Sci Monit 2024; 30:e944927

In Press

Clinical Research  

Percutaneous Coronary Intervention as a Non-Surgical Treatment for Ischemic Mitral Regurgitation in Patient...

Med Sci Monit In Press; DOI: 10.12659/MSM.943122  

Clinical Research  

Maxillary Canine Impaction: Assessing the Influence of Maxillary Anatomy Using Cone Beam Computed Tomography

Med Sci Monit In Press; DOI: 10.12659/MSM.944306  

Clinical Research  

Optimal Duration of Cold and Heat Compression for Forearm Muscle Biomechanics in Mixed Martial Arts Athlete...

Med Sci Monit In Press; DOI: 10.12659/MSM.944149  

Clinical Research  

A Retrospective Study of the Presentation, Diagnosis, Management, and Outcomes of 27 Patients with Osteogen...

Med Sci Monit In Press; DOI: 10.12659/MSM.944364  

Most Viewed Current Articles

17 Jan 2024 : Review article  

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  

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  

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  

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