烟气影响他莫昔芬及吲哚昔芬在大鼠肿瘤组织分布的机制
Effects of cigarette smoke on the distribution of Tamoxifen and Endoxifen in rat tumor tissues
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收稿日期： 年卷（期）页码：2020,35(02):-153-157
期刊名称：华西药学杂志
Journal Name：WEST CHINA JOURNAL OF PHARMACEUTICAL SCIENCES
关键字：乳腺癌;吸烟;他莫昔芬;吲哚昔芬;乳腺癌耐药蛋白;组织分布;大鼠乳腺癌模型;LC-MS/MS
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中文摘要
目的研究烟气对他莫昔芬及吲哚昔芬在大鼠肿瘤组织分布的影响机制。方法将50只甲基亚硝基脲诱导的♀SD模型大鼠随机分为对照组与吸烟试验组,均单剂量10 mg·kg(-1)他莫昔芬灌胃,通过LC-MS/MS检测血浆和肿瘤组织中他莫昔芬和吲哚昔芬的浓度,通过qRT-PCR和Western blot检测肿瘤组织中乳腺癌耐药蛋白(Bcrp) mRNA和蛋白水平的表达。结果 HE染色显示:对照组肿瘤组织出现浸润性乳腺癌细胞特征;试验组中血浆和肿瘤组织中待测物浓度均降低;试验组肿瘤组织Bcrp mRNA水平和蛋白水平均显著高于对照组。结论烟气通过诱导肿瘤组织Bcrp的表达,减少了他莫昔芬、吲哚昔芬在肿瘤组织中的分布;吲哚昔芬受到Bcrp外排作用影响,可能是Bcrp的底物。
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