Sotrastaurin attenuates the stemness of gastric cancer cells by targeting PKCδ

Biomed Pharmacother. 2019 Sep;117:109165. doi: 10.1016/j.biopha.2019.109165. Epub 2019 Jun 28.


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.

Keywords: Adriamycin; Chemoresistance; Gastric cancer stemness; PKCδ; Sotrastaurin.

MeSH terms

  • Cell Line, Tumor
  • Doxorubicin / pharmacology
  • Drug Resistance, Neoplasm / drug effects
  • Humans
  • Neoplasm Metastasis
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / enzymology*
  • Neoplastic Stem Cells / pathology*
  • Protein Kinase C-delta / metabolism*
  • Pyrroles / pharmacology*
  • Quinazolines / pharmacology*
  • Stomach Neoplasms / enzymology*
  • Stomach Neoplasms / pathology*


  • Pyrroles
  • Quinazolines
  • sotrastaurin
  • Doxorubicin
  • Protein Kinase C-delta