12 June 2016 : Laboratory Research
DNA Repair Genes ERCC1 and BRCA1 Expression in Non-Small Cell Lung Cancer Chemotherapy Drug Resistance
Shuai WangBC, Feng LiuCD, Jingyan ZhuDE, Peng ChenEF, Hongxing LiuFG, Qi LiuBG, Junqing HanABCDDOI: 10.12659/MSM.896606
Med Sci Monit 2016; 22:1999-2005
Abstract
BACKGROUND: Surgery combined with chemotherapy is an important therapy for non-small cell lung cancer (NSCLC). However, chemotherapy drug resistance seriously hinders the curative effect. Studies show that DNA repair genes ERCC1 and BRCA1 are associated with NSCLC chemotherapy, but their expression and mechanism in NSCLC chemotherapy drug-resistant cells has not been elucidated.
MATERIAL AND METHODS: NSCLC cell line A549 and drug resistance cell line A549/DDP were cultured. Real-time PCR and Western blot analyses were used to detect ERCC1 and BRCA1 mRNA expression. A549/DDP cells were randomly divided into 3 groups: the control group; the siRNA-negative control group (scramble group); and the siRNA ERCC1 and BRCA1siRNA transfection group. Real-time PCR and Western blot analyses were used to determine ERCC1 and BRCA1 mRNA and protein expression. MTT was used to detect cell proliferation activity. Caspase 3 activity was tested by use of a kit. Western blot analysis was performed to detect PI3K, AKT, phosphorylated PI3K, and phosphorylated AKT protein expression.
RESULTS: ERCC1 and BRCA1 were overexpressed in A549/DDP compared with A549 (P<0.05). ERCC1 and BRCA1siRNA transfection can significantly reduce ERCC1 and BRCA1 mRNA and protein expression (P<0.05). Downregulating ERCC1 and BRCA1 expression obviously inhibited cell proliferation and increased caspase 3 activity (P<0.05). Downregulating ERCC1 and BRCA1 significantly decreased PI3K and AKT phosphorylation levels (P<0.05).
CONCLUSIONS: ERCC1 and BRCA1 were overexpressed in NSCLC drug-resistant cells, and they regulated lung cancer occurrence and development through the phosphorylating PI3K/AKT signaling pathway.
Keywords: Antineoplastic Combined Chemotherapy Protocols - pharmacology, A549 cells, BRCA1 Protein - genetics, Carcinoma, Non-Small-Cell Lung - genetics, DNA Repair - genetics, DNA-Binding Proteins - genetics, Down-Regulation - drug effects, Drug Resistance, Neoplasm - genetics, Endonucleases - genetics, Lung Neoplasms - genetics, RNA, Messenger - genetics, Real-Time Polymerase Chain Reaction
Editorial
01 May 2024 : Editorial
Editorial: First Regulatory Approval for Adoptive Cell Therapy with Autologous Tumor-Infiltrating Lymphocytes (TILs) – Lifileucel (Amtagvi)DOI: 10.12659/MSM.944927
Med Sci Monit 2024; 30:e944927
In Press
11 Mar 2024 : Clinical Research
Enhancement of Frozen-Thawed Human Sperm Quality with Zinc as a Cryoprotective AdditiveMed Sci Monit In Press; DOI: 10.12659/MSM.942946
12 Mar 2024 : Database Analysis
Risk Factors of Age-Related Macular Degeneration in a Population-Based Study: Results from SHIP-TREND-1 (St...Med Sci Monit In Press; DOI: 10.12659/MSM.943140
12 Mar 2024 : Clinical Research
Preoperative Blood Transfusion Requirements for Hemorrhoidal Severe Anemia: A Retrospective Study of 128 Pa...Med Sci Monit In Press; DOI: 10.12659/MSM.943126
12 Mar 2024 : Clinical Research
Tissue Inhibitors of Metalloproteinase 1 (TIMP-1) and 3 (TIMP-3) as New Markers of Acute Kidney Injury Afte...Med Sci Monit In Press; DOI: 10.12659/MSM.943500
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
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
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