ReferenceID 3463

Cryptotanshinone inhibits human glioma cell proliferation in vitro and in vivo through SHP-2-dependent inhibition of STAT3 activation

Cell Death Dis

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 stud

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Reference Id
3463
Evidence Id
20053
Core Evidence Id
20053
Source Reference Id
230
Herb2 Reference Id
HBREF000438
Subject Paper Key
HBIN021795_28492557
Pubmed Id
28492557
Doi
10.1038/cddis.2017.174
Paper Title
Cryptotanshinone inhibits human glioma cell proliferation in vitro and in vivo through SHP-2-dependent inhibition of STAT3 activation
Paper Abstract
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.
Journal
Cell Death Dis
Publish Year
2017
Experiment Subject
human glioma cell ,nude mice bearing intracerebral u87 xenografts,
Experiment Type
Animal & Cell Experiment
Phenotype Related
Paper Title Cn
Paper Title En
Cryptotanshinone inhibits human glioma cell proliferation in vitro and in vivo through SHP-2-dependent inhibition of STAT3 activation
Bilingual Status
semi_complete