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
作者:曾金;郑亮;李蓉;贾米;徐苗;温成铭;何思言;王凌;蒋学华;
Author:
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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基金项目:
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。
参考文献
[1] Hoffmann D,Hecht SS.Advances in tobacco carcinogenesis[J].Chemi Carcinog Mutagen I,1990,94(1):63-102.
[2] Ambrosone CB,Freudenheim JL,Graham S,et al.Cigarette smoking,N-acetyltransferase 2 genetic polymorphisms,and breast cancer risk[J].JAMA J,1996,276(18):1494-1501.
[3] Xue F,Willett WC,Rosner BA,et al.Cigarette smoking and the Incidence of breast cancer[J].Archi Intern Med,2011,171(2):125-133.
[4] Jordan VC.Tamoxifen:Catalyst for the change to targeted therapy[J].Eur J Cancer,2008,44(1):30-38.
[5] 张磊,秦克旺.他莫西芬及其活性代谢物Endoxifen的研究进展[J].中华乳腺病杂志(电子版),2011,5(4):493-498.
[6] 柳慧星,王燕忠,于海涛,等.雌激素受体阳性乳腺癌他莫昔芬耐药机制的研究进展[J].肿瘤,2015,35(9):1039-1044.
[7] Sheelendra Pratap S,Raju KSR,Ali MM,et.al.Reduced bioavailability of tamoxifen and its metabolite 4-hydroxytamoxifen after oral administration with biochanin a (an isoflavone) in rats[J].Phytother Res,2012,26(2):303-307.
[8] Sayyed K,Vee ML,Abdel-Razzak Z,et al.Alteration of human hepatic drug transporter activity and expression by cigarette smoke condensate[J].Toxicology,2016,363-364:58-71.
[9] Gullino PM,Pettigrew HM,Grantham FH.N-Nitrosomethylurea as Mammary Gland Carcinogen in Rats[J].J National Cancer Inst,1975,54(2):401-414.
[10] 汤永峰,谢莉莉,冯晓敏,等.PTEN、p53和EGFR在乳腺癌中的表达与临床意义[J].现代肿瘤医学,2014,22(2):345-349.
[11] 王瑞芬,黄坊,孙和国,等.α-SMA和MMP-9在乳腺癌中的表达及意义[J].诊断病理学杂志,2013,20(2):91-93,96.
[12] 邢洲,张惠,胡慧贤,等.CCL18与TGF-β促进乳腺癌EMT的比较[J].暨南大学学报:自然科学与医学版,2016,37(5):367-371.
[13] Teft WA,Mansell SE,Kim RB.Endoxifen,the active metabolite of tamoxifen,is a substrate of the efflux transporter P-glycoprotein (Multidrug Resistance 1)[J].Drug Metab Dispos,2011,39(3):558-562.
[14] Liu M,Poo WK,Lin YL.Pyrazine,2-ethylpyridine,and 3-ethylpyridine are cigarette smoke components that alter the growth of normal and malignant human lung cells,and play a role in multidrug resistance development[J].Exp Mol Pathol,2015,98(1):18-26.
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