Fig. 6

Hypothetical model illustrating the role and regulation of EGFR and ROS production in NSCLC cells. a In chemosensitive NSCLC cells: (1) CDDP treatment leads activation p53 at the site of Ser15; (2) this impairs the activation of EGFR and its downstream signaling cascades, PI3K and Akt; (3) Decreased Akt and activated p53 contribute together increase in CDDP-induced ROS production. b In chemoresistant NSCLC cells, (1) CDDP failed to activate p53; (2) EGFR can be activated and promotes its downstream PI3K-Akt signaling cascade; (3) Due to the absence of activated p53 and hyperactivated Akt, CDDP-induced ROS is decreased and in turn apoptosis is impaired. Solid line indicates activated molecular action whereas dashed line indicates suppressed signaling. Arrows indicates direct action whereas blocked line indicates inhibition