Fas Ligand Enhances Apoptosis of Human Lung Cancer Cells Cotreated with RIG-I-like Receptor Agonist and Radiation
| Autor: | Eichi Tsuruga, Hironori Yoshino, Yoshiaki Sato, Ikuo Kashiwakura |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Agonist Cancer Research Fas Ligand Protein Lung Neoplasms medicine.drug_class Cell Apoptosis RIG-I-like receptor Antiviral Agents Fas ligand 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Drug Discovery Tumor Cells Cultured medicine Humans Receptors Immunologic Receptor Cell Proliferation Pharmacology Gene knockdown Chemistry Chemoradiotherapy Poly I-C 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer research DEAD Box Protein 58 |
| Zdroj: | Current Cancer Drug Targets. 20:372-381 |
| ISSN: | 1568-0096 |
| Popis: | Background: Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) play key roles in the antiviral response, but recent works show that RLR activation elicits anticancer activity as well, including apoptosis. Previously, we demonstrated that the anticancer activity of the RLR agonist Poly(I:C)-HMW/LyoVec™ [Poly(I:C)-HMW] against human lung cancer cells was enhanced by cotreatment with ionizing radiation (IR). In addition, cotreatment with Poly(I:C)-HMW and IR induced apoptosis in a Fas-independent manner, and increased Fas expression on the cell surface. Objective: The current study investigated the resultant hypothesis that Fas ligand (FasL) may enhance apoptosis in lung cancer cells cotreated with Poly(I:C)-HMW+IR. Methods: FasL was added into culture medium at 24 h following cotreatment with Poly(I:C)- HMW+IR, after upregulation of cell surface Fas expression on human lung cancer cells A549 and H1299 have already been discussed. Results: FasL enhanced the apoptosis of A549 and H1299 cells treated with Poly(I:C)-HMW+IR. Similarly, IR alone - and not Poly(I:C)-HMW - resulted in the upregulation of cell surface Fas expression followed by a high response to FasL-induced apoptosis, thus suggesting that the high sensitivity of cells treated with Poly(I:C)-HMW+IR to FasL-induced apoptosis resulted from the cellular response to IR. Finally, knockdown of Fas by siRNA confirmed that the high response of treated cells to FasL-induced apoptosis is dependent on Fas expression. Conclusion: In summary, the present study indicates that upregulated Fas expression following cotreatment with Poly(I:C)-HMW and IR is responsive to FasL-induced apoptosis, and a combination of RLR agonist, IR, and FasL could be a potential promising cancer therapy. |
| Databáze: | OpenAIRE |
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