Fas Ligand Enhances Apoptosis of Human Lung Cancer Cells Cotreated with RIG-I-Like Receptor Agonist and Radiation

(E-pub Ahead of Print)

Author(s): Yoshiaki Sato, Hironori Yoshino*, Eichi Tsuruga, Ikuo Kashiwakura.

Journal Name: Current Cancer Drug Targets

Become EABM
Become Reviewer


Background: Retinoic acid inducible gene-I (RIG-I)-like receptors (RLRs) play key roles within 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 has already occurred.

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 depended on Fas expression.

Conclusion: In summary, the present study indicated that upregulated Fas expression following cotreatment with Poly(I:C)-HMW and IR was responsive to FasL-induced apoptosis, and combination of RLR agonist, IR, and FasL could be a potential promising cancer therapy.

Keywords: Apoptosis, Fas, Fas ligand, Ionizing radiation, Poly(I:C), Retinoic acid-inducible gene-I-like receptor

Rights & PermissionsPrintExport Cite as

Article Details

(E-pub Ahead of Print)
DOI: 10.2174/1568009620666200115161717
Price: $95

Article Metrics

PDF: 1