Cryptotanshinone potentiates the antitumor effects of doxorubicin on gastric cancer cells via inhibition of STAT3 activity.

Objective To investigate the synergistic effects of cryptotanshinone (CPT) and doxorubicin (DOXO) on induction of apoptosis in human gastric cancer cells and the mechanisms. Methods Cell proliferation and apoptosis were detected using the CCK8 assay and AnnexinV/PI staining, respectively. Western blotting was used to determine the levels and phosphorylation of proteins encoded by STAT3-regulated genes and the cleaved forms of caspases and PARP. Results CPT significantly potentiated the antiproliferative effect of DOXO in gastric cancer cell lines. CPT combined with DOXO induced apoptosis and cleavage of caspases-3,-7,-9 as well as PARP. CPT or a STAT3 siRNA significantly suppressed constitutive and IL-6-induced phosphorylation of STAT3 Tyr705, decreasing the levels of proteins encoded by STAT3-target genes (Bcl-xL, Mcl-1, survivin, and XIAP). Conclusions CPT enhanced the anticancer activity of DOXO in gastric cancer cells via STAT3 inactivation and suppression STAT3-regulated antiapoptotic gene expression, indicating that DOXO combined with CPT may serve as effective therapy for gastric cancer.