Monoamine oxidase A (MAO A) inhibitors decrease glioma progression.
Monoamine oxidase A (MAO A) inhibitors decrease glioma progression.
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DOI：
10.18632/oncotarget.7283
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发表时间：
2016-03-22
期刊：
影响因子：
--
通讯作者：
Shih JC
中科院分区：
文献类型：
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作者：
Kushal S;Wang W;Vaikari VP;Kota R;Chen K;Yeh TS;Jhaveri N;Groshen SL;Olenyuk BZ;Chen TC;Hofman FM;Shih JC
胶质母细胞瘤（GBM）是一种侵袭性脑肿瘤，目前用替莫唑胺（TMZ）治疗。肿瘤通常会对TMZ产生耐药性并复发;然后没有有效的治疗方法。单胺氧化酶A（MAO A）氧化单胺神经递质，产生导致癌症的活性氧。本研究表明，MAO A在人脑胶质瘤组织和细胞系中表达增加。单胺氧化酶A抑制剂，氯吉兰或近红外染料MHI-148共轭氯吉兰（NMI），细胞毒性的胶质瘤，并减少在体外的侵袭。使用颅内TMZ抗性胶质瘤模型，氯吉林或匪I单独或与低剂量TMZ组合减少肿瘤生长并增加动物存活。NMI特异性地定位于肿瘤。免疫细胞化学研究表明，MAO A抑制剂减少增殖，微血管密度和侵袭，并增加巨噬细胞浸润。总之，我们已经确定了MAO A抑制剂作为潜在的新型独立药物或作为与低剂量TMZ的组合疗法用于耐药胶质瘤。NMI也可以用作非侵入性成像工具。因此具有治疗和诊断的双重功能。
Glioblastoma (GBM) is an aggressive brain tumor which is currently treated with temozolomide (TMZ). Tumors usually become resistant to TMZ and recur; no effective therapy is then available. Monoamine Oxidase A (MAO A) oxidizes monoamine neurotransmitters resulting in reactive oxygen species which cause cancer. This study shows that MAO A expression is increased in human glioma tissues and cell lines. MAO A inhibitors, clorgyline or the near-infrared-dye MHI-148 conjugated to clorgyline (NMI), were cytotoxic for glioma and decreased invasion in vitro. Using the intracranial TMZ-resistant glioma model, clorgyline or NMI alone or in combination with low-dose TMZ reduced tumor growth and increased animal survival. NMI was localized specifically to the tumor. Immunocytochemistry studies showed that the MAO A inhibitor reduced proliferation, microvessel density and invasion, and increased macrophage infiltration. In conclusion, we have identified MAO A inhibitors as potential novel stand-alone drugs or as combination therapy with low dose TMZ for drug-resistant gliomas. NMI can also be used as a non-invasive imaging tool. Thus has a dual function for both therapy and diagnosis.