دورية أكاديمية
PI3K Catalytic Subunits α and β Modulate Cell Death and IL-6 Secretion Induced by Talc Particles in Human Lung Carcinoma Cells.
| العنوان: | PI3K Catalytic Subunits α and β Modulate Cell Death and IL-6 Secretion Induced by Talc Particles in Human Lung Carcinoma Cells. |
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| المؤلفون: | Bougen-Zhukov NM; Bioinformatics Institute, Agency for Science, Technology, and Research, Singapore, Singapore., Lee YY; Bioinformatics Institute, Agency for Science, Technology, and Research, Singapore, Singapore., Lee JJ; Bioinformatics Institute, Agency for Science, Technology, and Research, Singapore, Singapore., Lee P; Division of Respiratory and Critical Care, National University Hospital, National University Health System, Singapore, Singapore; and., Loo LH; Bioinformatics Institute, Agency for Science, Technology, and Research, Singapore, Singapore.; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. |
| المصدر: | American journal of respiratory cell and molecular biology [Am J Respir Cell Mol Biol] 2020 Mar; Vol. 62 (3), pp. 331-341. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Thoracic Society Country of Publication: United States NLM ID: 8917225 Publication Model: Print Cited Medium: Internet ISSN: 1535-4989 (Electronic) Linking ISSN: 10441549 NLM ISO Abbreviation: Am J Respir Cell Mol Biol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2000- : New York, NY : American Thoracic Society Original Publication: [New York, NY : The Association, [c1989- |
| مواضيع طبية MeSH: | Adenocarcinoma/*enzymology , Carcinoma, Non-Small-Cell Lung/*enzymology , Class II Phosphatidylinositol 3-Kinases/*physiology , Lung Neoplasms/*enzymology , Neoplasm Proteins/*physiology , Sclerosing Solutions/*pharmacology , Talc/*pharmacology , Transcription Factors/*physiology, Actins/physiology ; Adenocarcinoma/metabolism ; Adenocarcinoma/pathology ; Carcinoma, Non-Small-Cell Lung/metabolism ; Carcinoma, Non-Small-Cell Lung/pathology ; Cell Death ; Cell Line, Tumor ; Class II Phosphatidylinositol 3-Kinases/biosynthesis ; Class II Phosphatidylinositol 3-Kinases/genetics ; Drug Resistance ; Enzyme Induction ; Humans ; Interleukin-6/metabolism ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; Neoplasm Proteins/antagonists & inhibitors ; Pleural Effusion, Malignant/chemistry ; Protein Kinase Inhibitors/pharmacology ; Protein Subunits ; RNA Interference ; RNA, Messenger/biosynthesis ; RNA, Messenger/genetics ; RNA, Neoplasm/biosynthesis ; RNA, Neoplasm/genetics ; RNA, Small Interfering/genetics ; Signal Transduction ; Transcription Factors/antagonists & inhibitors ; Transcription Factors/biosynthesis ; Transcription Factors/genetics |
| مستخلص: | Hydrated magnesium silicate (or "talc" particles) is a sclerosis agent commonly used in the management of malignant pleural effusions, a common symptom of metastatic diseases, including lung cancers. However, the direct effects of talc particles to lung carcinoma cells, which can be found in the malignant pleural effusion fluids from patients with lung cancer, are not fully understood. Here, we report a study of the signaling pathways that can modulate the cell death and IL-6 secretion induced by talc particles in human lung carcinoma cells. We found that talc-sensitive cells have higher mRNA and protein expression of PI3K catalytic subunits α and β. Further experiments confirmed that modulation (inhibition or activation) of the PI3K pathway reduces or enhances cellular sensitivity to talc particles, respectively, independent of the inflammasome. By knocking down specific PI3K isoforms, we also confirmed that both PI3Kα and -β mediate the observed talc effects. Our results suggest a novel role of the PI3K pathway in talc-induced cell death and IL-6 secretion in lung carcinoma cells. These cellular events are known to drive fibrosis, and thus further studies of the PI3K pathway may provide a better understanding of the mechanisms of talc sclerosis in the malignant pleural space. |
| فهرسة مساهمة: | Keywords: cell death; lung cancer cells; malignant pleural effusion; pleurodesis; talc |
| المشرفين على المادة: | 0 (Actins) 0 (IL6 protein, human) 0 (Interleukin-6) 0 (Neoplasm Proteins) 0 (PI3KCA protein, human) 0 (Protein Kinase Inhibitors) 0 (Protein Subunits) 0 (RNA, Messenger) 0 (RNA, Neoplasm) 0 (RNA, Small Interfering) 0 (Sclerosing Solutions) 0 (Transcription Factors) 14807-96-6 (Talc) EC 2.7.1.137 (Class II Phosphatidylinositol 3-Kinases) EC 2.7.1.137 (PIK3C2B protein, human) |
| تواريخ الأحداث: | Date Created: 20190913 Date Completed: 20200727 Latest Revision: 20200727 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1165/rcmb.2019-0050OC |
| PMID: | 31513749 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1535-4989 |
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| DOI: | 10.1165/rcmb.2019-0050OC |