title: Poly(I:C) exhibits an anti-cancer effect in human gastric adenocarcinoma cells which is dependent on RLRs.
abstract: 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 effect in 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.
authors.affiliation: Institute of Immunopharmacology and Immunotherapy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, China. Electronic address: qujing861105@163.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Qu
authors.forename: Zhaohua
authors.initials: Z
authors.lastname: Hou
authors.forename: Qiuju
authors.initials: Q
authors.lastname: Han
authors.forename: Cai
authors.initials: C
authors.lastname: Zhang
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tian
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D053487:DEAD-box RNA Helicases / Q000235:genetics; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011070:Poly I-C / Q000494:pharmacology* / Q000627:therapeutic use; D020365:RNA Helicases / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C437968:PLAAT4 protein, human; D018168:Receptors, Retinoic Acid; C520569:DHX58 protein, human; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D020365:RNA Helicases; D011070:Poly I-C
keywords: Apoptosis; Bcl-2; Human gastric adenocarcinoma; LGP2; MDA-5; Poly(I:C); RIG-I; RLRs; laboratory of genetics and physiology 2; melanoma differentiation associated factor 5; polyinosinic–polycytidylic acid; retinoic acid inducible gene I-like receptors; retinoic acid-inducible gene I