Journal
JOURNAL OF INTERNATIONAL MEDICAL RESEARCH
Volume 45, Issue 1, Pages 220-230Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/0300060516685513
Keywords
Human gastric cancer; cryptotanshinone; doxorubicin; STAT3
Funding
- Natural Science Foundation of Zhejiang Province, China [LY13H290014]
- National Natural Science Foundation of China [81473389, 81403199, 81503581]
- Special Foundation of Science Technology Department of Zhejiang Province [2012C13017-1]
- Specialized Research Fund for the Doctoral Program of Higher Education [20123322 110001]
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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.
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