Fig. 7: A model for venlafaxine (VEN) antagonizing the NE-promoted colon cancer progression by inhibiting NET.

By binding with beta-adrenergic receptor (b-AR), norepinephrine (NE) induces Akt activation, VEGF expression, cell proliferation, angiogenesis, and cancer progression in human colorectal cancer (CRC) cells. NE also increases the expression of NE transporter (NET). Venlafaxine (VEN) can antagonize the above effects of NE by inhibiting the NE-increased NET expression, which is related to the interaction of NET and protein phosphatase 2 scaffold subunit alpha (PPP2R1A).