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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.

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