Transcriptional regulation of seven cyadox-related genes mainly activated by PI3K and NF-кB signaling pathways in PK-15 cells

Cyadox, a new antibacterial agent as the quinoxaline-1, 4-dioxides, has a good antibacterial and growth-promoting effect, and has the advantages of lower toxicity, adequate safety and faster absorption. Seven differential expressed genes (DEGs) induced by cyadox were screened in swine liver tissues, including Insulin-like Growth Factor-1 (IGF-1), Epidermal Growth Factor (EGF), Poly ADP-ribose polymerase (PARP), the Defender Against Apoptotic Death 1 (DAD1), Complement Component 3 (C3), Transketolase (TK) and cyadox-related novel gene (CRNG). To elucidate the signal mechanism that cyadox altered these genes expression, the time-effect relationship and signaling pathways related to 7 DEGs induced by cyadox were determined in Porcine Kidney-15 (PK-15) cells by RT-qPCR and the application of various signal pathway inhibitors. The phosphorylation levels of signal factors in PK-15 cells were detected by Western blot. The analyses demonstrated that, the mRNA expressions of 7 DEGs were significantly enhanced by cyadox mainly through the phosphoinositide 3-kinase (PI3K) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-кB) signaling pathways in PK-15 cells. Furthermore, EGF might be the early response gene of cyadox to activate downstream signaling pathways and regulates the expression of other related genes or directly exerting biological effects. In brief, cyadox mainly regulates the expression of these 7 genes by PI3K and NF-кB signaling pathways to exert it's antibacterial and growth-promoting activity in PK-15 cells.