Antitumor effect of dimethyl itaconate on thymic carcinoma by targeting LDHA-mTOR axis
Antitumor effect of dimethyl itaconate on thymic carcinoma by targeting LDHA-mTOR axis
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DOI：
10.1016/j.lfs.2021.119847
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发表时间：
2021-07-21
期刊：
影响因子：
6.1
通讯作者：
Chida, Masayuki
中科院分区：
文献类型：
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作者：
Hayashi, Keitaro;Nakazato, Yoshimasa;Chida, Masayuki
目的：胸腺癌是一种罕见的癌症，没有既定的标准药物治疗。研究衣康酸二甲酯（DI）对人胸腺癌细胞株的抗肿瘤作用。主要方法：以人胸腺癌细胞株Ty82为研究对象，观察DI对细胞活力的影响。采用Western blotting和免疫组织化学方法研究DI对Ty82细胞的抗肿瘤作用机制。关键发现：DI抑制Ty82的细胞生长并促进其凋亡。DI对Ty82的抑制作用是通过下调乳酸脱氢酶A（LDHA）以及随后降低雷帕霉素的机械靶点（mTOR）的活性来介导的。DI与大中性氨基酸转运蛋白1（LAT1）的特异性抑制剂具有协同抗肿瘤作用，LAT1是一种氨基酸转运蛋白，目前正被研究作为癌症治疗的新靶点。意义：我们的研究结果表明，DI是一种新的潜在的策略，胸腺癌的治疗。
Aims: Thymic carcinoma is a rare type of cancer without an established standard pharmaceutical treatment. This study investigated the antitumor effect of dimethyl itaconate (DI), a cell-permeable derivative of itaconate, on human thymic carcinoma cell line. Main methods: Human thymic carcinoma cell line Ty82 was used to evaluate the effect of DI on cell viability. Western blotting and immunohistochemistry were performed to determine the molecular mechanism of anti-tumor effects of DI on Ty82. Key findings: DI suppressed cell growth and promoted apoptosis of Ty82. The suppressive effect of DI on Ty82 was mediated by the downregulation of lactate dehydrogenase A (LDHA), and the subsequent decrease in the activity of mechanistic target of rapamycin (mTOR). DI exhibited synergistic antitumor effects with a specific inhibitor of large neutral amino acid transporter 1 (LAT1), an amino acid transporter currently being investigated as a novel target for cancer therapy. Significance: Our findings demonstrate that DI is a novel potential strategy for thymic carcinoma treatment.