Sotrastaurin attenuates the stemness of gastric cancer cells by targeting PKCδ

treatment failure. Cancer stem cells (CSCs) have been proven to be essential for cancer metastasis and chemoresistance. PKC delta (protein kinase C-delta), a novel member of PKC family, has been validated as a synthetic lethal target in multiple cancers, and contributes to tyrosine kinase inhibitors (TKI) resistance in EGFR-mutant NSCLC (non-small cell lung cancer) patients. However, its role in GC is unclear. Here, we systematically investigate its role in GC, especially in regulating GC stem cell-like properties. We found that PKC delta positively regulated the metastasis, chemoresistance, and stem cell-like characteristics of GC cells, and its inhibitor sotrastaurin could rescue the above effects mediated by PKC delta. Importantly, sotrastaurin could also weaken metastasis, chemoresistance, and stem cell-like characteristics of adriamycin-resistant GC cells via PKC delta suppression, indicating sotrastaurin is an ideal candidate for combinational therapy to overcome chemoresistance for GC.