RESUMO
While there were certain studies focusing on the mechanism of TGF-ß promoting the growth of glioma cells, the present work revealed another novel mechanism that TGF-ß may promote glioma cell growth via enhancing Nodal expression. Our results showed that Nodal expression was significantly upregulated in glioma cells when TGF-ß was added, whereas the TGF-ß-induced Nodal expression was evidently inhibited by transfection Smad2 or Smad3 siRNAs, and the suppression was especially significant when the Smad3 was downregulated. Another, the attenuation of TGF-ß-induced Nodal expression was observed with blockade of the ERK1/2 pathway also. Further detection of the proliferation, apoptosis, and invasion of glioma cells indicated that Nodal overexpression promoted the proliferation and invasion of tumor cells and inhibited their apoptosis, resembling the effect of TGF-ß addition. Downregulation of Nodal expression via transfection Nodal-specific siRNA in the presence of TGF-ß weakened the promoting effect of the latter on glioma cells growth, and transfecting Nodal siRNA alone in the absence of exogenous TGF-ß more profoundly inhibited the growth of glioma cells. These results demonstrated that while both TGF-ß and Nodal promoted glioma cells growth, the former might exert such effect by enhancing Nodal expression, which may form a new target for glioma therapy.
Assuntos
MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Glioma/enzimologia , Glioma/patologia , Proteína Nodal/metabolismo , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Neoplasias Encefálicas/enzimologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioma/genética , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Invasividade Neoplásica , Proteína Nodal/genéticaRESUMO
BACKGROUND: Headache have been recognized as major causes of public ill-health, whereas there currently are the limitations of conventional therapies available. Chuanxiong Chadiao Powder (CXCP) is a well-known classic TCM herbal prescription with respect to treating headache for more than 1000 years. The objective of this study is to systematically assess the clinical efficacy and safety of CXCP for headache. METHODS: A systematic literature search in four databases, up to May of 2014, was performed to identify randomized controlled trials (RCTs), which compared CXCP monotherapy or adjunct therapy with western conventional medicine (WCM) or placebo for headache. The primary outcome measures were headache frequency, headache duration, pain intensity scales, globe assessment, patients self report outcomes, and quality of life. The second outcome measures were the total clinical effective rate and adverse events. The methodological quality of RCTs was assessed independently based on the 7 criteria recommended by the Cochrane Back Review Group. RESULTS: A total of 3680 participants were included in 37 eligible studies. The methodological quality was generally poor and there was only one high quality trial. Meta-analyses of the studies found that significant effects of CXCP for improving headache frequency and headache duration and the total clinical effective rate compared with WCM or placebo control in treating headache (P<0.01). Adverse event monitoring was reported in 22 studies (59%), while the other 15 studies (41%) did not mentioned. CONCLUSIONS: The evidence from present study is supported but limited for CXCP clinical use in the management of headache because of methodological flaws. Larger sample-sizes and rigorously designed RCTs are required in the future.