Department of Clinical Pharmacy, Yijishan Hospital of Wannan Medical College, Anhui Provincial Center for Drug Clinical Evaluation, Wuhu, Anhui 241001, P.R. China.
State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, Jiangsu 21009, P.R. China.
Oncol Rep. 2017 Aug;38(2):1124-1132. doi: 10.3892/or.2017.5727. Epub 2017 Jun 16.
Overexpression lentivirus platform was established of OATP1B1 (organic anion transporting polypeptides 1B1) wild‑type and mutant type genetic polymorphism in vitro, and using this platform we investigated and compared the uptake of tamoxifen and its metabolites by mutating the 388 and the 521 bases. The overexpression lentivirus cell platforms were successfully constructed, including OATP1B11a-HEK293T and OATP1B11b-HEK293T and OATP1B15-HEK293T cell model, the infection efficiency is not less than 80%. It shows a high level of gene expression at the mRNA and protein level. The tamoxifen and endoxifen can be taken up into the cells through organic anion transporter polypeptide 1B1, and OATP1B1521T>C inhibits the function of the transport protein, resulting in the content of drug in cell lysis liquid in OATP1B15-HEK293T group is lower than in OATP1B11a-HEK293T group (tamoxifen or endoxifen), with statistical significance. The content of the drug in cell lysis liquid in OATP1B11b-HEK293T group and the OATP1B1*1a-HEK293T group, similar with no statistical significance. These results suggest that tamoxifen and endoxifen can be transported by OATP1B1. However, OATP1B1 521T>C can inhibit the effects of OATP1B1 on tamoxifen and endoxifen in the cells.
建立了 OATP1B1（有机阴离子转运多肽 1B1）野生型和突变型遗传多态性的过表达慢病毒平台，并利用该平台研究和比较了突变 388 和 521 个碱基对时他莫昔芬及其代谢物的摄取情况。成功构建了过表达慢病毒细胞平台，包括 OATP1B11a-HEK293T 和 OATP1B11b-HEK293T 和 OATP1B15-HEK293T 细胞模型，感染效率不低于 80%。它在 mRNA 和蛋白质水平上显示出高水平的基因表达。他莫昔芬和内消旋他莫昔芬可通过有机阴离子转运多肽 1B1 摄取到细胞中，并且 OATP1B1521T>C 抑制转运蛋白的功能，导致 OATP1B15-HEK293T 组细胞裂解液中药物含量低于 OATP1B11a-HEK293T 组（他莫昔芬或内消旋他莫昔芬），具有统计学意义。OATP1B11b-HEK293T 组和 OATP1B1*1a-HEK293T 组细胞裂解液中药物含量相似，无统计学意义。这些结果表明他莫昔芬和内消旋他莫昔芬可被 OATP1B1 转运。然而，OATP1B1 521T>C 可抑制 OATP1B1 对细胞中他莫昔芬和内消旋他莫昔芬的作用。
