Molecular characterization of the organic anion transporter family

发展靶向癌症化疗的一种方法是利用肿瘤细胞对药剂的吸收增加。在这种情况下，高浓度的药物在癌细胞中负责差异杀伤，而在正常人细胞中的低浓度降低了副作用。我们已经建立了LST-1和LST-2重组腺病毒，称为AdLST-1和AdLST-2。使用SCID小鼠在皮下肿瘤模型中估计MTX与腺病毒组合的体内作用。用AdLST-1/MTX或AdLST-2/MTX处理的肿瘤比用Adβ-gal/MTX处理的肿瘤生长缓慢。全身放射自显影证实，在用AdLST-1/MTX和AdLST 2/MTX处理的小鼠肿瘤中，[^3H]-MTX掺入。我们的观察结果强烈支持这样的可能性，即内流泵的过度表达是增强癌症化疗的新途径。

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.