FIGURE 2.

HIF‐1α and VEGF are downstream of TLR4, baicalein reduces HIF‐1α and VEGF expressions in TLR4‐dependent manner. (A) Drug–Targets–Disease network illustrates the overlapping targets between CRC and baicalein (yellow nodes) and the target‐related pathways (green nodes). (B) Protein‐protein interaction network showing the interaction between the candidate protein targets of baicalein and (C) the number of proteins interact with the highlighted protein. (F) CRISPR/Cas9‐mediated knockout of TLR4 in HCT116 cells (TLR4KO‐116). (D‐E) Protein expressions of HIF‐1α and VEGF in CRC cells (HCT116, TLR4‐overexpressed (TLR4‐116), TLR4KO‐116, DLD‐1, TLR4‐overexpressed DLD‐1 (TLR4‐DLD)). Expressions of p‐NF‐κB, HIF‐1α, and VEGF in HCT116 and DLD‐1 cells in the (G‐H) presence of LPS or (I‐J) absence of LPS after baicalein or TLR4 inhibitor C34 treatment. (K‐N) Protein expressions of HIF‐1α and VEGF in TLR4‐116, TLR4‐DLD, and TLRKO‐116 cells after baicalein or C34 treatment. Shown is mean ± SE, n = 3 individual experiments, *P < 0.05, **P < 0.01 compared to control. TLR4, toll‐like receptor 4; HIF‐1α, hypoxia‐inducible factor 1‐alpha; VEGF, vascular endothelial growth factor