Affiliation:
1. Department of Radiation Science, Hirosaki University Graduate School of Health Sciences, Hirosaki, Aomori 036- 8564, Japan
Abstract
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.
Funder
Japan Society for the Promotion of Science
Publisher
Bentham Science Publishers Ltd.
Subject
Cancer Research,Drug Discovery,Pharmacology,Oncology
Cited by
6 articles.
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