2021 Fiscal Year Final Research Report
Mechanism of multidrug resistance acquisition by transcriptional regulators involved in lung cancer metastasis
Project/Area Number |
20K22717
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Research Category |
Grant-in-Aid for Research Activity Start-up
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Allocation Type | Multi-year Fund |
Review Section |
0801:Pharmaceutical sciences and related fields
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Research Institution | Takasaki University of Health and Welfare |
Principal Investigator |
ZHANG XIEYI 高崎健康福祉大学, 薬学部, 博士研究員 (60878510)
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Project Period (FY) |
2020-09-11 – 2022-03-31
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Keywords | 上皮間葉転換 / 薬物排出系トランスポーター / 足場タンパク / SNAIファミリー / がん転移 / 転写調節因子 / 肺がん / HCC827肺がん細胞 |
Outline of Final Research Achievements |
Multidrug resistance-associated protein 2 (MRP2) is a drug efflux transporter involved in multidrug resistance in cancer. In the present study, we determined whether the transcriptional regulator Slug is involved in MRP2 activity. mRNA and protein expression levels of MRP2 in Slug-transfected HCC827 lung cancer cells were significantly higher compared to Mock. The intracellular uptake of CDCF and SN-38 levels in Slug-transfected HCC827 cells were significantly decreased compared to Mock cells. Furthermore, there was a high correlation between Slug and MRP2 mRNA expression levels in lung cancer patients. This study demonstrates that Slug plays a regulatory role in MRP2 expression and function.
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Free Research Field |
生物薬剤学
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Academic Significance and Societal Importance of the Research Achievements |
P-糖タンパク質(P-gp)や乳がん耐性タンパク質(BCRP)、多剤耐性タンパク質2(MRP2)は細胞膜上に局在して薬物を細胞外に排出するトランスポーター(ETPs) であり、がんの多剤耐性に関与している。今までにがんの多剤耐性を抑制する目的でP-gpの阻害薬の開発が進められてきたが、他の手段を用いて多剤耐性を抑制する研究はほとんど行われていない。本研究は、肺がん細胞および肺がん臨床検体において、転写調節因子Slugが足場タンパク質を介さずに直接MRP2の発現量増強に寄与している可能性を見出した。この研究結果より、転写調節因子発現の制御から多剤耐性の制御できる医薬品の創製が期待された。
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