Figure 4. Effects of imatinib alone or in combination with oridonin on growth-signaling pathways in SUP-B15 cells. The SUP-B15 cells were incubated with 1μM imtinib for 6, 12, 24 h, or with 1 μM imatinib plus 3 μM oridonin for 24 h. They were then harvested and total proteins were extracted. Equal amounts of protein from each sample were separated on SDS-PAGE and immunoblotted with indicated antibodies, GAPDH was used as a loading control. Imatinib upregulated Akt/mTOR signaling pathway (A), inhibited constitutively activation of MEK, ERK signaling proteins (C) and STAT5 signaling (E) and had no significant effect on RAF and LYN signaling proteins (C,E). Oridonin overcame the upregulation of Akt/mTOR signaling pathway by imatinib. (B), Oridonin plus imatinib had no synergetic inhibitory effects on activation of MEK, ERK (D) and STAT5 (F) signaling proteins. The combination of oridonin and imatinib exerted significant inhibitory effect on activation of LYN tyrosine kinase (F). The results shown were representative of two independent experiments.