【摘 要】
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Recent evidence shows that the expression levels of histamine receptor H3(Hrh3)are upregulated in several types of cancer.However,the role of Hrh3 in non-small cell lung cancer(NSCLC)has not been elucidated.In the present study,we showed that the expressi
【机 构】
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Department of Translation Medicine Center,Key Laboratory of Clinical Cancer Pharmacology and Toxicol
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Recent evidence shows that the expression levels of histamine receptor H3(Hrh3)are upregulated in several types of cancer.However,the role of Hrh3 in non-small cell lung cancer(NSCLC)has not been elucidated.In the present study,we showed that the expression levels of Hrh3 were significantly increased in NSCLC samples,and high levels of Hrh3 were associated with poor overall survival(OS)in NSCLC patients.In five human NSCLC cell lines tested,Hrh3 was significantly upregulated.In NSCLC cell lines H1975,H460,and A549,Hrh3 antagonist ciproxifan(CPX,10-80 μM)exerted moderate and concentration-dependent inhibition on the cell growth and induced apoptosis,whereas its agonist RAMH(80 μM)reversed these effects.Furthermore,inhibition of Hrh3 by CPX or siRNA retarded the migration and invasion of NSCLC cells through inhibiting epithelial-mesenchymal transition(EMT)progression via reducing the phosphorylation of PI3K/Akt/mTOR and MEK/ERK signaling pathways.In nude mice bearing H1975 cell xenograft or A549 cell xenograft,administration of CPX(3 mg/kg every other day,intraperitoneal)significantly inhibited the tumor growth with increased E-cadherin and ZO-1 expression and decreased Fibronectin expression in tumor tissue.In conclusion,this study reveals that Hrh3 plays an important role in the growth and metastasis of NSCLC;it might be a potential therapeutic target against the lung cancer.
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