Cryptotanshinone inhibits human glioma cell proliferation in vitro and in vivo through SHP-2-dependent inhibition of STAT3 activation.
Cryptotanshinone inhibits human glioma cell proliferation in vitro and in vivo through SHP-2-dependent inhibition of STAT3 activation.
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隐丹参酮通过 SHP-2 依赖性抑制 STAT3 激活，在体外和体内抑制人胶质瘤细胞增殖
DOI：
10.1038/cddis.2017.174
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发表时间：
2017-05-11
影响因子：
9
通讯作者：
Shen X
中科院分区：
文献类型：
--
作者：
Lu L;Zhang S;Li C;Zhou C;Li D;Liu P;Huang M;Shen X
恶性神经胶质瘤（MG）是成人最常见的原发性脑癌之一，具有较高的死亡率和复发率。因此，寻找更有效的治疗MG的方法已变得非常紧迫。本文研究了隐丹参酮（cryptotanshinone，CTS）在体内外对MG的影响，并探讨了其作用机制。体外观察CTS对细胞增殖、周期、迁移和侵袭的影响。Western blot和免疫荧光染色检测JAK/STATs信号通路的激活。使用SHP-2抑制剂或SiRNA来确定SHP-2的参与。用荷瘤裸鼠脑内移植瘤U87研究CTS的体内抗MG活性。结果表明，CTS通过抑制STAT 3信号通路，显著抑制MG体外增殖。细胞周期阻滞于G 0/G1期。尽管CTS没有改变总SHP-2蛋白的表达，但在体内和体外，CTS处理以剂量依赖的方式增加SHP-2蛋白的酪氨酸磷酸酶活性。SHP-2抑制剂或SiRNA可逆转CTS对STAT 3 Tyr 705磷酸化的抑制作用。体内实验表明，CTS能抑制颅内肿瘤的生长，延长荷瘤裸鼠的生存期，证实了CTS对MG的抑制作用。本研究结果提示CTS可能是一种潜在的MG治疗药物。CTS的抑制作用主要归因于通过上调SHP-2蛋白酪氨酸磷酸酶活性的新机制抑制STAT 3 Tyr 705磷酸化。
Malignant gliomas (MGs) are one of the most common primary brain cancers in adults with a high mortality rate and relapse rate. Thus, finding better effective approaches to treat MGs has become very urgent. Here, we studied the effects of cryptotanshinone (CTS) on MGs in vitro and in vivo, and explored the underlying mechanisms. Effects of CTS in vitro on cell proliferation, cycle, migration and invasion were evaluated. The activation of JAK/STATs signaling was detected by western blot and immunofluorescenc staining. SHP-2 inhibitor or SiRNA were used to determine the involvement of SHP-2. The in vivo anti-MGs activity of CTS was studied with nude mice bearing intracerebral U87 xenografts. Our results revealed that CTS significantly inhibited the proliferation of MGs in vitro via inhibiting STAT3 signal pathway. The cell cycle was arrested at G0/G1 phase. Although CTS did not change the expression of total SHP-2 protein, the tyrosine phosphatase activity of SHP-2 protein was increased by CTS treatment in a dose-dependent manner in vivo and in vitro. SHP-2 inhibitor or SiRNA could reverse the inhibitory effect of CTS on phosphorylation of STAT3 Tyr705. In vivo study also showed that CTS inhibited the intracranial tumor growth and extended survival of nude mice bearing intracerebral U87 xenografts, confirming an inhibitory effect of CTS on MGs. Our results indicated CTS may be a potential therapeutic agent for MGs. The inhibitory action of CTS is largely attributed to the inhibition of STAT3 Tyr705 phosphorylation with a novel mechanism of upregulating the tyrosine phosphatase activity of SHP-2 protein.
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DOI：
10.1158/1541-7786.mcr-09-0313
发表时间：
2009-11
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Dabir S;Kluge A;Dowlati A
通讯作者：
Dowlati A
隐丹参酮通过抑制雌激素受体信号传导来抑制乳腺癌细胞生长。
影响因子：
3.6
作者：
Li, Shanhu;Wang, Hongtao;Zhou, Jianguang
通讯作者：
Zhou, Jianguang
DOI：
10.2174/157488908786242489
发表时间：
2008-11-01
期刊：
Recent patents on CNS drug discovery
影响因子：
--
作者：
Heimberger, Amy B;Priebe, Waldemar
通讯作者：
Priebe, Waldemar
DOI：
10.2174/1871520615666150907093036
发表时间：
2016-01-01
影响因子：
2.8
作者：
Hao, Wenhui;Zhang, Xuenong;Chen, Xiuping
通讯作者：
Chen, Xiuping
影响因子：
1.9
作者：
Cuevas, P;Diaz-González, D;Dujovny, M
通讯作者：
Dujovny, M