Gastric cancer (GC) is one of the most lethal malignancies. Chemoresistance and metastasis are the main cause of treatment failure. Cancer stem cells (CSCs) have been proven to be essential for cancer metastasis and chemoresistance. PKCδ (protein kinase C-δ), 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 PKCδ positively regulated the metastasis, chemoresistance, and stem cell-like characteristics of GC cells, and its inhibitor sotrastaurin could rescue the above effects mediated by PKCδ. Importantly, sotrastaurin could also weaken metastasis, chemoresistance, and stem cell-like characteristics of adriamycin-resistant GC cells via PKCδ suppression, indicating sotrastaurin is an ideal candidate for combinational therapy to overcome chemoresistance for GC.
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| http://dx.doi.org/10.1016/j.biopha.2019.109165 | DOI Listing |
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