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KAKEN_17H03583seika.pdf
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xCT阻害剤による小細胞肺癌のフェロトーシス誘導機構の解明とその抗腫瘍効果の検討
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xCT ソガイザイ ニ ヨル ショウサイボウ ハイガン ノ フェロトーシス ユウドウ キコウ ノ カイメイ ト ソノ コウシュヨウ コウカ ノ ケントウ
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xCT sogaizai ni yoru shōsaibō haigan no ferotōshisu yūdō kikō no kaimei to sono kōshuyō kōka no kentō
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Elucidation of the mechanism of the induction of ferroptosis by xCT inhibitor and its antitumor effect in small cell lung cancer
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永野, 修
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ナガノ, オサム
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Nagano, Osamu
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慶應義塾大学・医学部 (信濃町) ・准教授
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Research team head
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科研費研究者番号 : 30404346
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2020
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科学研究費補助金研究成果報告書
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2019
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本研究では、小細胞肺癌のフェロトーシス感受性についての検討を行った。小細胞肺癌で発現低下し、フェロトーシス感受性と相関するマーカーとしてSLC7A1(xCT)、SLC3A2（CD98hc）、MALT1やBIRC3を同定した。xCTについてはヒト肺癌組織検体を用いた免疫染色を行い、xCT発現が低いことを確認した。さらに、小細胞肺癌の動物モデルであるRPMマウスより腫瘍オルガノイドを作製し、フェロトーシス誘導剤の評価をすることができるマウスモデルを作製した。また、xCT阻害剤の非臨床試験を行い、SCLCにおいてxCT阻害によるフェロトーシス誘導治療が有効であるという非臨床POCが得られた。
In this study, we investigated the susceptibility of small cell lung cancer (SCLC) to ferroptosis. We identified SLC7A1 (xCT), SLC3A2 (CD98hc), MALT1 and BIRC3 as the markers that were downregulated in SCLC and correlated with susceptibility to ferroptosis. Furthermore, we performed immunostaining of xCT using a human lung cancer tissue sample and confirmed that xCT expression was low in SCLC. The tumor organoids were prepared from the RPM mouse, an animal model of SCLC, to establish a model to evaluate the impact of ferroptosis-inducing cancer therapy. Finally, we conducted a non-clinical study by using the xCT inhibitor and obtained a POC in which the ferroptosis-inducing therapy is effective treatment for SCLC.
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研究種目 : 基盤研究 (B) (一般)
研究期間 : 2017～2019
課題番号 : 17H03583
研究分野 : 腫瘍生物学
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