Cryptotanshinone potentiates the antitumor effects of doxorubicin on gastric cancer cells via inhibition of STAT3 activity.
Cryptotanshinone potentiates the antitumor effects of doxorubicin on gastric cancer cells via inhibition of STAT3 activity.
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隐丹参酮通过抑制 STAT3 活性增强阿霉素对胃癌细胞的抗肿瘤作用
DOI：
10.1177/0300060516685513
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发表时间：
2017-03
期刊：
影响因子：
--
通讯作者：
Liu P
中科院分区：
文献类型：
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作者：
Wang J;Zhang G;Dai C;Gao X;Wu J;Shen L;Chen Z;Liu P
目的探讨隐丹参酮(CPT)与阿霉素(Doxo)协同诱导人胃癌细胞凋亡的作用及其机制。方法采用CCK8法检测细胞增殖，AnnexinV/PI染色检测细胞凋亡。Western blotting检测STAT3调控基因编码的蛋白质水平和磷酸化水平，以及caspase和PARP的裂解形式。结果CPT可明显增强Doxo对人胃癌细胞株的抗增殖作用。CPT联合Doxo可诱导caspase-3、-7、-9和PARP的凋亡和裂解。CPT或STAT3 siRNA显著抑制STAT3 Tyr705的组成性和IL-6诱导的磷酸化，降低STAT3靶基因(Bclxl、Mcl-1、Survivin和XIAP)编码的蛋白质水平。结论CPT通过抑制STAT3的失活和抑制STAT3调节的抗细胞凋亡基因的表达，增强了DOXO在胃癌细胞中的抗癌活性，提示DOXO联合CPT可能成为治疗胃癌的有效药物。
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.