title: Toll-like receptor 5 agonist inhibition of growth of A549 lung cancer cells in vivo in a Myd88 dependent manner.
abstract: The purpose of this study was to examine the effect of a Toll-like receptor 5 (TLR5) agonist, CBLB502, on the growth and radiosensitivity of A549 lung cancer cells in vivo. Expression of myeloid differentiation factor 88 (MyD88) or TLR5 was stably knocked down in human lung cancer cells (A549) using lentivirus expressing short hairpin RNA targeting human MyD88 or TLR5. Lack of MyD88 or TLR5 expression enhanced tumor growth in mouse xenografts of A549 lung cancer cells. CBLB502 inhibited the growth of A549 lung cancer cells, not A549-MyD88-KD cells in vivo in the murine xenograft model. Our results showed that the inhibition of A549 by CBLB502 in vivo was realized through regulating the expression of neutrophil recruiting cytokines and neutrophil infiltration. Finally, we found that activation of TLR5 signaling did not affect the radiosensitivity of tumors in vivo.
authors.affiliation: Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Shi-Xiang
authors.initials: SX
authors.lastname: Zhou
authors.forename: Feng-Sheng
authors.initials: FS
authors.lastname: Li
authors.forename: Yu-Lei
authors.initials: YL
authors.lastname: Qiao
authors.forename: Xue-Qing
authors.initials: XQ
authors.lastname: Zhang
authors.forename: Zhi-Dong
authors.initials: ZD
authors.lastname: Wang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D011836:Radiation Tolerance / Q000187:drug effects; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D051198:Toll-Like Receptor 5 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays
chemical_list: C528306:CBLB502; D016207:Cytokines; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D010455:Peptides; D034741:RNA, Small Interfering; D011838:Radiation-Sensitizing Agents; C495346:TLR5 protein, human; D051198:Toll-Like Receptor 5