1. Interferon Regulatory Factor-1 Regulates Cisplatin-Induced Apoptosis and Autophagy in A549 Lung Cancer Cells
- Author
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Hua Yang, Yongzhong Luo, Tianli Cheng, Lemeng Zhang, Zhou Jiang, Xiaoping Wen, Jianhua Chen, and Huihuang Yi
- Subjects
Male ,Cancer Research ,Lung Neoplasms ,Cell Survival ,Apoptosis ,Antineoplastic Agents ,NSCLC ,Carcinoma, Non-Small-Cell Lung ,Autophagy ,Humans ,Medicine ,Lung cancer ,Aged ,Cell Proliferation ,Membrane Potential, Mitochondrial ,Cisplatin ,Original Paper ,IRF-1 ,business.industry ,Hematology ,General Medicine ,Middle Aged ,medicine.disease ,Oxidative Stress ,IRF1 ,Oncology ,A549 Cells ,Drug Resistance, Neoplasm ,Cancer research ,Female ,Reactive Oxygen Species ,business ,Interferon Regulatory Factor-1 ,medicine.drug - Abstract
Purpose: This study aimed to investigate the expression and function of interferon regulatory factor-1 (IRF-1) in non-small cell lung cancer (NSCLC). Methods: IRF-1 expression and its prognostic value were investigated through bioinformatic analysis. The protein expression levels of IRF-1, cleaved caspase-3, and LC3-I/II were analyzed by western blotting. A lentiviral vector was used to overexpress or knockdown IRF-1 in vitro. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were analyzed by JC-1 and DCFH-DA staining, respectively. ATP, SOD, MDA, cell viability, LDH release, and caspase-3 activity were evaluated using commercial kits. Results: Compared to the levels in normal tissues, IRF-1 expression was significantly lower in lung cancer tissues and was a prognostic factor for NSCLC. Cisplatin treatment induced IRF-1 activation, ROS production, ATP depletion, SOD consumption, and MDA accumulation in A549 lung cancer cells. IRF-1 overexpression promoted mitochondrial depolarization, oxidative stress, and apoptotic cell death and inhibited autophagy in A549 cells, and these effects could be reversed by IRF-1 knockdown. Conclusion: These data suggest that IRF-1 regulates apoptosis, autophagy and oxidative stress, which might be served as a potential target for increasing chemotherapy sensitivity of lung cancer.
- Published
- 2021