A natural anthraquinone derivative shikonin synergizes with AZD9291 against wtEGFR NSCLC cells through reactive oxygen species-mediated endoplasmic reticulum stress.

摘要: Abstract Background NSCLC is the major type of lung cancer and survival rates patients remain low. AZD9291 a third-generation EGFR-TKI approved to treat harboring EGFR T790M mutation common targetable activating mutations, but it has limited effect for wtEGFR NSCLC. Purpose The current study investigated whether shikonin could enhance antitumor in cells. Methods SRB colony formation assay were used detect proliferation cells, propidium iodide staining was performed apoptosis, ROS analyzed using DCFH-DA staining, western blot expression indicated proteins. Results We demonstrated that shikonin, natural inducer, In addition, increased AZD9291-induced apoptosis accompanying with generation activation ER stress. Furthermore, inhibition by NAC or GSH reversed induced plus AZD9291, recovered stress activated combination treatment, indicating mediated played vital role this therapy. Moreover, anticancer activity primary cells through ROS-mediated Conclusion Our suggests combining promising therapeutic strategy treating patients.