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| 1 | OCTN2 基因多态性影响结直肠癌奥沙利铂化疗敏感性显示文摘目的:研究OCTN2基因多态性是否影响OCTN2的表达和功能,以及结直肠癌细胞系SW480对奥沙利铂敏感性。方法:构建OCTN2基因4种突变(F17L、E317K、S467C和P478L)转染细胞系。Real-time RT-PCR及Western blot检测OCTN2 mRNA和蛋白水平的表达。HPLC检测细胞内奥沙利铂含量。MTS法检测细胞活性。结果:所有突变型OCTN2 mRNA和蛋白表达水平与野生型表达无统计学差异。E317K和S467C细胞系对奥沙利铂摄取(V_(max)和K_(m))与野生型相比无差异(P>0.05),F17L的V_(max)下降到66.4%,而K_(m)值增加到120.3%,P478L的V_(max)增加到132.6%,K_(m)值降低到82.2%,与野生型相比有统计学差异(P<0.05)。所有过表达OCTN2细胞的IC 50值显著降低。与SW480-OCTN2转染细胞系比较,没有转染的SW480细胞和F17L细胞系的IC 50值分别升高175%和147%,而P478L细胞则下降到76.9%,有统计学差异(P<0.05)。E317K和S467C的IC 50值无明显改变(P>0.05)。结论:OCTN2转运体基因F17L和P478L错义突变可以改变OCTN2对奥沙利铂的摄取,从而影响OCTN2稳定表达细胞系对奥沙利铂的敏感性。 | 鲁琼 朱海宏 戚听听 李国华 滕欣琪 屈强 屈健 | 2021 | 中国临床药理学与治疗学2021，26，4： | 2 |
| 2 | Special topic: Emerging role of transporters in drug interaction and delivery显示文摘To date,over 400 membrane transporters have been identified and characterized in human cells at both the molecular level and functional level.These transporters are classified into two families:ATP-binding cassette(ABC)transporters and solute carrier(SLC)transporters.They are well-recognized determinants of drug disposition and metabolism,even in the development of some diseases.Due to the biological function and tissue-specific expression,transporters play a potent role not only in drug disposition but also in drug-drug/drug-food interaction,and hold great potential to be utilized as targets for drug delivery.In 2019,we published a printed book entitled Drug Transporters(PMPH 2019;ISBN 978-7-117-28219-2)in Chinese.The content of the PMPH 2019 book included the basic transporter information and its role in diseases,drug-drug interaction,and drug delivery.However,the printed PMPH 2019 book was started in 2015.The field is growing so fast that several new emerging areas were uncovered in the book,which motivated us to propose a special issue that focuses on the latest advances of drug transporters in drug interaction and delivery.In this issue,we would like to invite several contributors to discuss the emerging findings regarding transporters and drugs. | Longfa Kou Zhonggui He Jin Sun | 2020 | Asian Journal of Pharmaceutical Sciences2020，15，2： | 0 |
| 3 | 孕酮对OCTN2的抑制作用及对左旋肉碱肾脏排泄的影响显示文摘目的考察孕酮对肉碱/有机阳离子转运体2(carnitine/organic cation transporter 2,OCTN2)功能的影响,并探讨其是否通过抑制肾脏OCTN2功能改变左旋肉碱肾脏排泄,从而降低妊娠期血浆左旋肉碱浓度。方法采用已构建的稳定高表达人OCTN2的MDCK-hOCTN2细胞模型,分别以米屈肼和氘代左旋肉碱为底物,考察孕酮对OCTN2的抑制作用。正常雌性ICR小鼠皮下注射孕酮,使其达妊娠晚期血清孕酮浓度,比较其与对照组小鼠左旋肉碱尿液排泄差异,以及血浆和各组织中左旋肉碱浓度差异。结果孕酮显著抑制OCTN2对米屈肼和氘代左旋肉碱的摄取,半数抑制浓度分别为8.7μmol·L^(-1)和14.0μmol·L^(–1)。孕酮给药组小鼠血清孕酮浓度为462~1153 nmol·L^(-1),与妊娠晚期生理浓度相当,左旋肉碱的尿液排泄量以及血浆、肝脏、肾脏和心脏中左旋肉碱浓度与对照组无显著差异。结论孕酮显著抑制OCTN2功能,但与妊娠晚期生理浓度相当的孕酮不影响左旋肉碱的肾脏排泄及体内稳态。 | 白梦如 陈铭扬 蒋惠娣 马志媛 | 2023 | 中国现代应用药学2023，40，2： | 0 |
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