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細胞内活性酸素が与えるトランスポーター制御を用いた乳がん治療への応用

寺崎, 梓 筑波大学

2021.08.03

概要

人をはじめとする全ての好気性生物は常に酸素無くして生きていくことはできない。生命維持に必要なエネルギーを得るために、ミトコンドリアで絶えず酸素を消費している。しかし、これらの酸素の⼀部は、代謝過程で活性酸素と呼ばれる反応性の高い状態に変換されることがある。このような活性分⼦種は極めて反応性に富み、生体内の構造や機能を破壊しうる。つまり、酸素は生命維持に必要であるにも関わらず、両刃の剣のごとく、時に自らをも傷つけることがある。このため、全ての好気性生物は、これらの活性酸素を消去する防衛機構を備えており、これをなくしては生存できない。したがって、生物進化の過程は、酸素の代謝利用の獲得と同時に、その毒性を消去する抗酸化機構も獲得してきた歴史でもあった。健康時には、これらの反応系が動的平衡状態にあり、調和の取れた生命現象を維持している。しかし、物理化学的または生物学的負荷がかかると、それらの平衡関係が崩れ、“酸化的ストレス”が生じ、細胞障害のみならず、時には生体の死をも招く結果となる。特に抗がん治療における化学療法や放射線療法などによる生体への物理化学的負荷は、非常に大きな酸素毒性を生じる。そのため、正常細胞においては有害事象を減らす上でこれらをいかに軽減するかが、がん細胞においては、酸素毒性による治療効果を期待することが臨床上の重要な課題である。

我々の研究室では、このような細胞内活性酸素関連機構と抗がん治療への応用について長らく研究を重ねている。本稿では、本来は生体内に有害であり、不要とされる活性酸素を用いた抗癌治療への応用についての研究の詳細を記し、さらに今後の展望について述べる。

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