Wogonoside inhibits TNF receptor-associated factor 6 (TRAF6) mediated-tumor microenvironment and prognosis of pancreatic cancer.

Pancreatic cancer (PC) is one of the worst prognostic cancers. Here, we probed the anti-cancer activity of wogonoside (Wog), a flavonoid isolated from Scutellaria baicalensis Georgi, on PC, as well as potential molecular mechanism. Following Wog stimulation, the viability, proliferation, apoptosis, stem cell-like transition, and mesenchymal transition were detected in PC cells. Bioinformatics analysis was used to identify possible signaling pathways involved in the anti-PC activity of Wog. Tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) was overexpressed and TRAF6 activator IL-1β was used in PC cells to confirm whether Wog exerted anti-PC activity via modulating TRAF6. In vivo, an experiment was conducted to further confirm our supposition. Wog inhibited PC cell proliferation, promoted cell apoptosis, limited PC cell stem cell-like transition and mesenchymal transition. TNF signaling pathway was activated in PC. Besides, Wog inactivated TRAF6/nuclear factor-kappa B (NF-κB)/p65 pathway in PC cells. TRAF6, vascular cell adhesion molecule-1 (VCAM1), CD44, and matrix metalloproteinase 14 (MMP14) expressions were upregulated in PC tissues and negatively correlated with PC survival and prognosis. Finally, Wog suppressed TRAF6 overexpression-induced PC cell stem cell-like transition and mesenchymal transition in vitro and tumor growth in vivo. Wog exerted anti-cancer activity on PC and suppressed the TRAF6 mediated-tumor microenvironment of PC, thereby regulating PC's prognosis.