Fig. 5: R406 targets Syk/PI3K pathway against Syk-positive GSCs.

a Western blot demonstrated that Syk is highly expressed in GSC-1 but not GSC-2, U87 or U251. Protein extracted from non-glioma tumor cell line SW620 and HepG-2 were positive and negative control for Syk expression respectively. b Syk-specific siRNA decreased Syk expression and inhibited the phosphorylation of PI3K and Akt, which resulted in the activation of caspase 3 and the cleavage of PARP in GSC-1. c Knock-down of Syk expression elevated basal and maximal OCR in GSC-1. d Depletion of Syk promoted the production of ROS in GSC-1. e Depletion of Syk using specific siRNA resulted in a substantial increase in the percentage of apoptotic cells in GSC-1. f Transient knock-down of PI3K inhibited the phosphorylation of PI3K and Akt, and triggered caspase activation and PARP cleavage in GSC-1. g Silencing PI3K increased basal and maximal OCR in GSC-1. h ROS accumulated after depletion of PI3K in GSC-1. i Knock-down of PI3K significantly induced apoptosis in GSC-1. (***p < 0.001, statistical difference compared to the scramble group.)