Poly(I:C) exhibits an anti-cancer effect in human gastric adenocarcinoma cells which is dependent on RLRs.
Poly(I:C) exhibits an anti-cancer effect in human gastric adenocarcinoma cells which is dependent on RLRs.
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DOI:
10.1016/j.intimp.2013.08.013
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发表时间:
2013-11
影响因子:
5.6
通讯作者:
Jing Qu;Zhaohua Hou;Qiuju Han;Cai Zhang;Z. Tian;Jian Zhang
中科院分区:
文献类型:
--
作者:
Jing Qu;Zhaohua Hou;Qiuju Han;Cai Zhang;Z. Tian;Jian Zhang
Poly(I:C), an agonist of TLR3 and RLRs, has been used as an immune adjuvant in clinical trials for many years. Although it has been found to trigger apoptosis in a variety of cancers, its mechanisms in human gastric adenocarcinoma is unclear. The purpose of this study was to assess the effect of poly(I:C) on human gastric adenocarcinoma cells. Our observations showed that intracellular delivery of poly(I:C) by liposomes had a pro-apoptotic effectin vitro, and significantly inhibited xenograft growth of human gastric adenocarcinoma in nude mice. Further investigations indicated that RLRs, as intrinsic RNA sensors, contributed to the poly(I:C)-triggered apoptotic effect through upregulation of RIG-I, MDA-5, and most significantly, LGP2, accompanied by increased expression of Bcl-2 family members. Conversely, this apoptotic effect was greatly reduced by silencing RIG-I, MDA-5, or LGP2. Although LGP2 is considered an innate immune negative regulator of RIG-I and MDA-5, it exhibited a positive regulatory effect on poly(I:C)-induced apoptosis in human gastric adenocarcinoma cells. These findings suggested that poly(I:C) may be a promising chemotherapeutic agent against human gastric adenocarcinoma.