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膠質(zhì)瘤對(duì)MPPa-PDT敏感性研究中ABCG2的作用

發(fā)布時(shí)間:2018-06-05 16:49

  本文選題:三磷酸腺苷結(jié)合轉(zhuǎn)運(yùn)蛋白G超家族成員 + 焦脫鎂葉綠酸甲酯。 參考:《中國(guó)癌癥雜志》2017年02期


【摘要】:背景與目的:三磷酸腺苷結(jié)合轉(zhuǎn)運(yùn)蛋白G超家族成員2(adenosine triphosphate-binding cassette superfamily G member 2,ABCG2)在多種腫瘤細(xì)胞中表達(dá),能通過(guò)外排抗癌藥物參與腫瘤耐藥。本研究的目的旨在探討人膠質(zhì)瘤細(xì)胞對(duì)焦脫鎂葉綠酸甲酯(pyropheophorbide-a methyl ester,MPPa)介導(dǎo)的光動(dòng)力療法(photodynamic therapy,PDT)殺傷效應(yīng)的敏感性及其與ABCG2的關(guān)系。方法:選取處于對(duì)數(shù)生長(zhǎng)期的膠質(zhì)瘤細(xì)胞株U87、A172,分別經(jīng)MPPa-PDT或MPPa-PDT+煙曲霉毒素C(fumitremorgin C,FTC)處理后,采用CCK-8法檢測(cè)細(xì)胞活性;采用蛋白[質(zhì)]印跡法(Western blot)檢測(cè)細(xì)胞內(nèi)ABCG2的表達(dá);流式細(xì)胞技術(shù)法檢測(cè)未光照前各組細(xì)胞內(nèi)MPPa的含量;AnnexinⅤ-FITC/PI雙染流式細(xì)胞術(shù)檢測(cè)細(xì)胞凋亡率;DCFH-DA染色觀察細(xì)胞內(nèi)活性氧(reactive oxygen species,ROS)的產(chǎn)生。結(jié)果:MPPa-PDT能抑制A172、U87細(xì)胞的活性,且呈一定的光能量依賴性,A172達(dá)到半數(shù)致死量所需光能量密度為U87的8倍;A172較U87細(xì)胞對(duì)MPPa-PDT不敏感;A172細(xì)胞內(nèi)高表達(dá)的ABCG2影響MPPa在細(xì)胞內(nèi)的聚集;抑制ABCG2后,不僅可以增強(qiáng)MPPa-PDT對(duì)A172細(xì)胞的殺傷作用,同時(shí)可增加MPPa-PDT觸發(fā)產(chǎn)生的ROS的量及細(xì)胞對(duì)MPPa的攝取。結(jié)論:人膠質(zhì)瘤細(xì)胞株A172對(duì)MPPa-PDT相對(duì)不敏感,并且產(chǎn)生這種現(xiàn)象的機(jī)制可能是ABCG2外排MPPa,減少M(fèi)PPa的細(xì)胞內(nèi)聚集,進(jìn)而減弱光敏劑活化后對(duì)腫瘤細(xì)胞的殺傷作用。
[Abstract]:Background & AIM: adenosine triphosphate binding transporter G superfamily member 2(adenosine triphosphate-binding cassette superfamily G member 2 (ABCG2) is expressed in a variety of tumor cells and can participate in tumor resistance through efflux anticancer drugs. The aim of this study was to investigate the cytotoxicity of human glioma cells to pyropheophorbide-a methyl paraphorbide-a photodynamic therapy (PDT) mediated by pyropheophorbide-a methyl and its relationship with ABCG2. Methods: after treated with MPPa-PDT or MPPa-PDT fumitremorgin Con FTCrespectively, the cell activity was detected by CCK-8 assay, and the expression of ABCG2 was detected by Western blot assay. Flow cytometry was used to detect the MPPA content and Annexin 鈪,

本文編號(hào):1982729

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