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, onthe growth and radiosensitivity of A549 lung cancer cells in vivo. Expression of myeloid differentiation factor88 (MyD88) or TLR5 was stably knocked down in human lung cancer cells (A549) using lentivirus expressingshort hairpin RNA targeting human MyD88 or TLR5. Lack of MyD88 or TLR5 expression enhanced tumorgrowth 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 ofA549 by CBLB502 in vivo was realized through regulating the expression of neutrophil recruiting cytokines andneutrophil infiltration. Finally, we found that activation of TLR5 signaling did not affect the radiosensitivity oftumors in vivo.