Diarylpentanoid,a curcumin analog,inhibits malignant meningioma growth in both in vitro and in vivo models  

作　　者：Anna Terasawa Kazuhiro Shimazu Hiroshi Nanjo Masatomo Miura Hiroyuki Shibata 

机构地区：[1]Department of Clinical Oncology,Akita University,Akita 010-8543,Japan [2]Department of Clinical Oncology,Akita University Graduate School of Medicine,Akita 010-8543,Japan [3]Department of Pathology,Akita University,Akita 010-8543,Japan [4]Department of Pharmacokinetics,Graduate School of Medicine,Akita University,Akita,Japan

出　　处：《World Journal of Experimental Medicine》2025年第2期171-184,共14页世界实验医学杂志(英文)

基　　金：Supported by TAIHO Pharmaceutical,No.AS2023A000122715;Nippon Kayaku,No.NKCS20230416001.

摘　　要：BACKGROUND Malignant meningioma metastasizes systemically,primarily due to its role in epithelial-mesenchymal transition.Although the prognosis is extremely poor,drug development efforts have been limited,because this tumor is categorized as a rare form.AIM To examine growth suppressive effect of GO-Y030,a diarylpentanoid curcumin analog,(1E,4E)-1,5-bis[3,5-bis(methoxymethoxy)phenyl]penta-1,4-dien-3-one against the malignant meningioma.METHODS The growth suppression of malignant meningioma cells by GO-Y022 and GOY030 were examined,using IOMM-Lee and HKBMM cell lines.Male nude mice aged eight weeks,specifically BALB/cSlc-nu/nu mice received a subcutaneous inoculation of IOMM-Lee(107 cells/site)on their back and 30μg/kg of recombinant hepatocellular growth factor(HGF)was injected into the tumor every three days.After confirmed the growth tumor mass,500μL of GO-Y030 diluted with PBS were administrated intraperitoneally daily at doses of 1 mg/kg and 2 mg/kg,respectively.RESULTS GO-Y030 exhibits a growth inhibitory effect on malignant meningioma cell lines,IOMM-Lee and HKBMM ranging from 0.8-2.0μM in vitro.Notably,GO-Y030’s inhibitory effect is about 10 to 16th times more potent than that of curcumin,which has previously demonstrated potential in combating malignant meningioma.In mouse models,the intraperitoneal administration of GO-Y030 effectively suppresses the growth of malignant meningioma tumors that have been inoculated in the back(P=0.002).High-performance liquid chromatography analysis has confirmed the distribution of GO-Y030 in the bloodstream and brain tissue.Moreover,GOY030 demonstrates the ability to significantly suppress HGF(P<0.01),nuclear factor kappa B(P<0.001),and Ncadherin(P<0.001),all of which contribute to the epithelial-mesenchymal transition.CONCLUSION GO-Y030 holds promise as a potent compound for the systemic inhibition of malignant meningioma.GO-Y030 has higher tumor growth inhibitory effect against meningiomas than curcumin,which is known to have antitumor activity through multi-molec

关 键 词：Malignant meningioma CURCUMIN Diarylpentanoid curcumin analog Hepatocellular growth factor Nuclear factor kappa B N-CADHERIN 

分 类 号：R739.4[医药卫生—肿瘤]