2005 Fiscal Year Final Research Report Summary
Functional regulation and clinical application of the organic anion transporter LST family.
| Project/Area Number |
16390038
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
ABE Takaaki Tohoku University, Hospital, Lecturer, 病院, 講師 (80292209)
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| Project Period (FY) |
2004 – 2005
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| Keywords | gastrointestinal cancers / LST / organic anion transporter / MTX / adenovirus |
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| Research Abstract |
In the last decade, many transporters have been isolated, characterized their distribution and substrates. Among them, the organic anion transporter OATP family, transport bile acids, hormones as well as eicosanoids and various compounds (BSP, HMG-CoA reductase inhibitor, angiotensin converting enzyme inhibitor, etc.). So far, applicant isolated more than 15 clones of the oatp family firstly in the world and reported. We have isolated the organic anion transporter OATP/LST family which exclusively expressed in various gastrointestinal cancers.
Thenm we established LST-2 recombinant adenoviruses, termed 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-2/MTX grew more slowly than those treated with Adβ-gal/MTX. Whole-body autoradiograph 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. We also raised a ligand-screening method using adenovirus and fluorescent lignd of LST-2. This system unable us to screening various compounds preferable to transported by LST-2.
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