title: TLR3 dsRNA agonist inhibits growth and invasion of HepG2.2.15 HCC cells.
abstract: Toll-like receptor 3 (TLR3) is a pattern-recognizing receptor that is involved             in immune signaling and plays a crucial role in survival by being able to recognize             various viral components including double-stranded RNA (dsRNA). TLR3 expression             and function in cancer cells are not well understood. In this study, we investigated             whether TLR3 agonist dsRNA (BM-06) can inhibit proliferation and invasion, and             promote apoptosis in HepG2.2.15 cells. HepG2.2.15 cells secreting hepatitis B             virus (HBV) were treated with BM-06 and poly(I:C). Western blot analysis and PCR             were employed to determine pharmacodynamic changes in biomarkers relevant to TLR3             signaling. Cell proliferation, invasion and apoptosis were analyzed by CCK-8 assay,             transwell assay and flow cytometry. The expression of HBsAg, and HBcAg was observed             by immunohistochemistry. Compared with untreated cells, pharmacological NF-κB             activity of the TLR3 pathway by BM-06 (1.734-fold) or poly(I:C) (1.377-fold) was             induced. By western blot analysis, we found that dsRNA induced TLR3-activated             HepG2.2.15 cells which expressed NF-κB levels predominantly in the cytoplasmic             fraction but fewer signals in the nucleus. BM-06 inhibited the proliferation,             invasion and secretion of HBV, and induced apoptosis in HepG2.2.15 cells. In addition,             the antitumor effects of BM-06 were superior to poly(I:C). Pharmacological activation             of the TLR3 pathway by BM-06 can inhibit HepG2.2.15 cell growth.
authors.affiliation: Department of Pathology, Nantong Tumor Hospital, Nantong, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Yu-Yin
authors.initials: YY
authors.lastname: Xu
authors.forename: Jia-Ming
authors.initials: JM
authors.lastname: Zhou
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Wu
authors.forename: Qun
authors.initials: Q
authors.lastname: E
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D056945:Hep G2 Cells; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000378:metabolism; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000378:metabolism; D006515:Hepatitis B virus / Q000502:physiology; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000494:pharmacology*; D051196:Toll-Like Receptor 3 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D057074:Virus Release
chemical_list: D000970:Antineoplastic Agents; C574691:BM-06; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D016328:NF-kappa B; D012330:RNA, Double-Stranded; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D011070:Poly I-C