title: Cryptotanshinone potentiates the antitumor effects of doxorubicin on gastric cancer cells via inhibition of STAT3 activity.
abstract: 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.
authors.affiliation: 1 The Criminal Science and Technology Department, Zhejiang Police College, Hangzhou, PR China.
authors.forename: Jiye
authors.initials: J
authors.lastname: Wang
authors.affiliation: 3 College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, PR China.
authors.forename: Guangji
authors.initials: G
authors.lastname: Zhang
authors.affiliation: 2 Zhejiang Key Laboratory of Gastro-Intestinal Pathophysiology, Zhejiang Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou, PR China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Dai
authors.affiliation: 2 Zhejiang Key Laboratory of Gastro-Intestinal Pathophysiology, Zhejiang Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou, PR China.
authors.forename: Xiufei
authors.initials: X
authors.lastname: Gao
authors.affiliation: 1 The Criminal Science and Technology Department, Zhejiang Police College, Hangzhou, PR China.
authors.forename: Jianbin
authors.initials: J
authors.lastname: Wu
authors.affiliation: 4 Center of Post-doctoral Studies, China Academy of Chinese Medicine Science, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.affiliation: 2 Zhejiang Key Laboratory of Gastro-Intestinal Pathophysiology, Zhejiang Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou, PR China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Chen
authors.affiliation: 2 Zhejiang Key Laboratory of Gastro-Intestinal Pathophysiology, Zhejiang Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou, PR China.
authors.forename: Pei
authors.initials: P
authors.lastname: Liu
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D004338:Drug Combinations; D004357:Drug Synergism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics / Q000378:metabolism; D010616:Phenanthrenes / Q000494:pharmacology*; D010766:Phosphorylation; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics / Q000378:metabolism; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; C494811:BCL2L1 protein, human; C107489:BIRC5 protein, human; D004338:Drug Combinations; D051034:Inhibitor of Apoptosis Proteins; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D010616:Phenanthrenes; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D051020:bcl-X Protein; C037886:cryptotanshinone; D004317:Doxorubicin; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases
keywords: Human gastric cancer; STAT3; cryptotanshinone; doxorubicin