Fig 5. ODE modeling of WNT5A-EGF/AR signaling and experimental validation.
(A) The effect of WNT5A on 22RV1 cell viability. (B) The effect of EGF on 22RV1 cell viability. (C) The effect of WNT5A and EGF on protein levels of Skp2, pERK, pAKT and AR. (D) The network topology of androgen-independent pathways in prostate cancer cells. WNT5A or EGF regulates the cellular proliferation by activating AR-related pathway. This network was represented as a series of ODE equations shown in Eq. (1–6) in the section “Materials and methods”. (E) The predicted values of four proteins fit the observation data well. (F, G) The ODE system-predicted PC proliferation at 72 hours perturbed by WNT5A (F) or EGF (G) with different doses. (H, I) Sensitivity analysis of the ODE system was performed under two conditions: WNT5A treatment only (H), and EGF treatment only (I). Each parameter was perturbed by increasing or decreasing 5%.