Berberine and Curcumin Target Survivin and STAT3 in Gastric Cancer Cells and Synergize Actions of Standard Chemotherapeutic 5-Fluorouracil

Nutr Cancer. 2015;67(8):1293-304. doi: 10.1080/01635581.2015.1085581. Epub 2015 Oct 22.


Aberrantly expressed survivin and STAT3 signaling have emerged as major determinants of chemoresistance in gastric cancer. We evaluated effects of potent herbal derivatives curcumin, berberine, and quercetin on STAT3 signaling, survivin expression, and response to 5-fluorouracil (5-FU) treatment in gastric cancer cells (AGS). Cytotoxic and inhibitory effects of berberine, curcumin, and quercetin alone or in combination with 5-FU were examined by MTT assay, and their effect on survivin, STAT3, and the phosphorylated active STAT3 (pSTAT3) expression was examined by western blotting. Effect of these herbal derivatives on STAT3 DNA binding activity was measured by electrophoretic mobility shift assay. Curcumin, berberine, and quercetin effectively downregulated pSTAT3 levels, survivin expression, and gastric cancer cells viability in a dose-dependent manner (with corresponding IC50 values of 40.3μM, 29.2μM and 37.5μM, respectively). Berberine was more effective in inhibiting survivin expression as compared to other herbal agents. 5-FU in combination with berberine or curcumin showed a synergistic inhibition of survivin and STAT3 level resulting in enhanced cell death in gastric cancer cells. Overall, our data suggest use of berberine and curcumin as adjunct therapeutics to overcome chemoresistance during treatment of gastric malignancies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Berberine / pharmacology*
  • Berberine / therapeutic use
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Curcumin / pharmacology*
  • Curcumin / therapeutic use
  • DNA / metabolism
  • Drug Resistance, Neoplasm / drug effects
  • Drug Synergism
  • Fluorouracil / therapeutic use*
  • Humans
  • Inhibitor of Apoptosis Proteins / antagonists & inhibitors*
  • Inhibitor of Apoptosis Proteins / drug effects
  • NF-kappa B / metabolism
  • Quercetin / pharmacology
  • STAT3 Transcription Factor / antagonists & inhibitors*
  • STAT3 Transcription Factor / drug effects
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects
  • Stomach Neoplasms / drug therapy*
  • Survivin


  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • NF-kappa B
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Survivin
  • Berberine
  • DNA
  • Quercetin
  • Curcumin
  • Fluorouracil