Molecular characterization of the organic anion transporter family

有机阴离子转运蛋白家族的分子表征

• 批准号: 14370777
• 负责人: ABE Takaaki
• 金额: $ 8.77万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370777/
• 关键词: organic anion transporter; LST-2; cancer; Methothrexate; adenovirus; 抗癌剤; メトトレキセート; ホルモン

One approach to the development of targeted cancer chemotherapy exploits increased uptake of the agent into neoplastic cells. In this scenario, higher concentrations of the agent in cancer cells are responsible for differential killing while the low concentration in normal human cells decreases side effects.We have isolated the organic anion transporter OATP/LST family which exclusively expressed in various gastrointestinal cancers. We have established LST-1 and LST-2 recombinant adenoviruses, termed AdLST-1 and AdLST-2. In vivo effects of the combination of MTX with the adenoviruses were estimated in a subcutaneous tumor model using SCID mice. Tumors treated with AdLST-1/MTX or AdLST-2/MTX grew more slowly than those treated with Adβ-gal/MTX. Whole-body autoradiographs confirmed that incorporation of [^3H]-MTX in tumors of mice treated with AdLST-1/MTX and AdLST2/MTX. Our observations strongly support the possibility that overexpression of influx pumps is a new avenue in the enhancement of cancer chemotherapy.

开发靶向癌症化疗的一种方法是增加肿瘤细胞对药物的吸收。在这种情况下，癌细胞中浓度较高的药物是造成差异杀伤的原因，而正常人类细胞中浓度较低的药物则减少了副作用。我们分离出了有机阴离子转运蛋白OATP/LST家族，该家族在多种胃肠道肿瘤中均有表达。我们建立了LST-1和LST-2重组腺病毒，分别命名为AdLST-1和AdLST-2。在使用SCID小鼠的皮下肿瘤模型中估计了MTX与腺病毒联合使用的体内效应。用AdLST-1/MTX或AdLST-2/MTX治疗的肿瘤比用Adβ-gal/MTX治疗的肿瘤生长更慢。全身放射自显像证实，AdLST-1/MTX和AdLST2/MTX治疗的小鼠肿瘤中存在[^3H]-MTX的掺入。我们的观察结果有力地支持了内流泵的过表达是增强癌症化疗的新途径的可能性。

项目成果

Suzuki T, Onogawa T, Unno M, Abe T et al.: "Identification and characterization of novel rat and human gonad specific organic anion transporters."Mol.Endocrinol.. 17. 1203-1215 (2003)

Suzuki T、Onokawa T、Unno M、Abe T 等人：“新型大鼠和人类性腺特异性有机阴离子转运蛋白的鉴定和表征。”Mol.Endocrinol.. 17. 1203-1215 (2003)

Mikkaichi T, Suzuki T, Unno M, Abe T et al.: "Isolation and characterization of novel kidney-specific digoxin transporters."Proc.Natl.Acad.Sci.USA. 101. 2569-3574 (2004)

Mikkaichi T、Suzuki T、Unno M、Abe T 等人：“新型肾脏特异性地高辛转运蛋白的分离和表征。”Proc.Natl.Acad.Sci.USA。

Mikkaichi T, Suzuki T, Unnno M, Abe T et al.: "Isolation and characterization of novel kidney-specific digoxin transporters"Proc.Natl.Acad.Sci.USA. 101. 3569-3574 (2004)

Mikkaichi T、Suzuki T、Unnno M、Abe T 等人：“新型肾脏特异性地高辛转运蛋白的分离和表征”Proc.Natl.Acad.Sci.USA。

Kodawara T, Masuda S, Abe T et al.: "Organic anion transporter oatp2-mediated interaction between dioxin and amiodarone in the rat liver"Pharmaceutical Res.. 19. 738-743 (2002)

Kodawara T、Masuda S、Abe T 等：“有机阴离子转运蛋白 oatp2 介导的大鼠肝脏中二恶英和胺碘酮之间的相互作用”Pharmaceutical Res.. 19. 738-743 (2002)

Tanemoto M, Abe T, Ito S, et al.: "Successful treatment of severe hypertension with combination of angiotensin converting enzyme inhibitor and angiotensin II receptor blocker."Hypertension Res.. 26. 863-868 (2003)

Tanemoto M、Abe T、Ito S 等人：“联合使用血管紧张素转换酶抑制剂和血管紧张素 II 受体阻滞剂成功治疗严重高血压。”高血压研究 26. 863-868 (2003)