Vorinostat and metformin sensitize EGFR-TKI resistant NSCLC cells via BIM-dependent apoptosis induction.

作者: Hengyi Chen , Yubo Wang , Caiyu Lin , Conghua Lu , Rui Han

DOI: 10.18632/ONCOTARGET.21225

关键词: Close relationshipApoptosis inductionMetforminVorinostatApoptosisPharmacologyGefitinibEgfr tkiMedicineAutophagy

摘要: There is a close relationship between low expression of BIM and resistance to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). Vorinostat pan-histone deacetylase (HDACi) that augments in various types tumor cells, however, this effect attenuated by the high anti-apoptotic proteins EGFR-TKI resistant non-small cell lung cancer (NSCLC) cells. combination with metformin - compound can inhibit expression, might cooperate activate apoptotic signaling overcome resistance. This study aimed investigate cooperative evaluate possible molecular mechanisms. The results showed vorinostat combined gefitinib augmented increased sensitivity NSCLC cells gefitinib, adding simultaneously could obviously proteins, further levels BAX, as result, improved both on intrinsic acquired EGFR-TKI. In addition, autophagy induced be significantly suppressed metformin, which also contribute enhance apoptosis improve gefitinib. These suggested represent novel strategy associated BIM-dependent larger heterogeneous populations.

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