阿魏酸通过 ROS/JNK/Bax 线粒体凋亡途径调控 GSDMD,诱导肺癌中的脓毒症

IF 2.2 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Current pharmaceutical biotechnology Pub Date : 2024-09-18 DOI:10.2174/0113892010303032240902063213
Xingchen Liu, Xin Zhang, Lida Mi, Hailin Zhang, Woda Shi
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引用次数: 0

摘要

背景:为改善肺癌患者的预后结果,仍需进行更多的研究。以前的报道已经证实了阿魏酸(FA)在肺癌中的作用,因此我们试图探究阿魏酸在肺癌中应用的更多分子机制。方法:采用 CCK8 和菌落形成实验探讨细胞活力和增殖。通过流式细胞术评估细胞凋亡。用显微镜观察细胞形态。用 JC-1 评估 MMP,用相对试剂盒评估 LDH 活性。通过 Western 印迹分析检测 GSDMD、GSDMD-N、caspase 家族蛋白和 ROS/JNK/Bax 线粒体凋亡通路下游蛋白的表达水平。流式细胞术分析也测量了 ROS 的水平。对动物模型的组织进行了 C-caspase-1 的 IHC 分析。结果研究发现,FA 能抑制肺癌细胞增殖、改变细胞形态、降低 MMP 和增强 LDH 活性,这表明它能诱导肺癌细胞发生热休克。研究发现,Caspase-1和GSDMD都参与了用FA处理的肺癌细胞的热解过程,其中Caspase-1介导了GSDMD。此外,还验证了 FA 在体外和体内通过 ROS/JNK/Bax 线粒体凋亡途径调控热凋亡。结论综上所述,FA通过ROS/JNK/Bax线粒体凋亡途径调控GSDMD,诱导肺癌细胞的热凋亡,这可能为肺癌发生中的热凋亡提供了理论依据。
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Ferulic Acid Regulates GSDMD through the ROS/JNK/Bax Mitochondrial Apoptosis Pathway to Induce Pyroptosis in Lung Cancer
Background: To improve the prognosis outcome of lung cancer patients, more investigations are still needed. Previous reports have demonstrated the function of Ferulic Acid (FA) in lung cancer; thus, we have attempted to probe more molecular mechanisms underlying FA application in lung cancer. Methods: CCK8 and colony formation experiments have been employed to explore cell viability and proliferation. Cell apoptosis was evaluated through flow cytometry. Cell morphology was observed with a microscope. MMP was assessed by JC-1 and LDH activity was evaluated by relative kit. Western blot assays were performed to examine the expression levels of GSDMD, GSDMD-N, caspase family proteins, and ROS/JNK/Bax mitochondrial apoptosis pathway downstream proteins. Flow cytometry analysis also measured the level of ROS. Tissues from animal models were taken for IHC analysis of C-caspase-1. Results: FA was found to inhibit proliferation, change cell morphology, decrease MMP, and enhance LDH activity, suggesting its ability to induce pyroptosis of lung cancer cells. Both caspase-1 and GSDMD were found to be involved in the pyroptosis of lung cancer cells treated with FA, and caspase-1 mediated GSDMD. Moreover, FA was validated to regulate pyroptosis by ROS/JNK/Bax mitochondrial apoptosis pathway in vitro and in vivo. Conclusion: In summary, FA regulates GSDMD through ROS/JNK/Bax mitochondrial apoptosis pathway to induce pyroptosis in lung cancer cells, which may offer a theoretical basis for pyroptosis in the occurrence of lung cancer.
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来源期刊
Current pharmaceutical biotechnology
Current pharmaceutical biotechnology 医学-生化与分子生物学
CiteScore
5.60
自引率
3.60%
发文量
203
审稿时长
6 months
期刊介绍: Current Pharmaceutical Biotechnology aims to cover all the latest and outstanding developments in Pharmaceutical Biotechnology. Each issue of the journal includes timely in-depth reviews, original research articles and letters written by leaders in the field, covering a range of current topics in scientific areas of Pharmaceutical Biotechnology. Invited and unsolicited review articles are welcome. The journal encourages contributions describing research at the interface of drug discovery and pharmacological applications, involving in vitro investigations and pre-clinical or clinical studies. Scientific areas within the scope of the journal include pharmaceutical chemistry, biochemistry and genetics, molecular and cellular biology, and polymer and materials sciences as they relate to pharmaceutical science and biotechnology. In addition, the journal also considers comprehensive studies and research advances pertaining food chemistry with pharmaceutical implication. Areas of interest include: DNA/protein engineering and processing Synthetic biotechnology Omics (genomics, proteomics, metabolomics and systems biology) Therapeutic biotechnology (gene therapy, peptide inhibitors, enzymes) Drug delivery and targeting Nanobiotechnology Molecular pharmaceutics and molecular pharmacology Analytical biotechnology (biosensing, advanced technology for detection of bioanalytes) Pharmacokinetics and pharmacodynamics Applied Microbiology Bioinformatics (computational biopharmaceutics and modeling) Environmental biotechnology Regenerative medicine (stem cells, tissue engineering and biomaterials) Translational immunology (cell therapies, antibody engineering, xenotransplantation) Industrial bioprocesses for drug production and development Biosafety Biotech ethics Special Issues devoted to crucial topics, providing the latest comprehensive information on cutting-edge areas of research and technological advances, are welcome. Current Pharmaceutical Biotechnology is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments.
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