Fluvastatin is effective against thymic carcinoma
Fluvastatin is effective against thymic carcinoma
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氟伐他汀对胸腺癌有效
DOI：
10.1016/j.lfs.2019.117110
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发表时间：
2020
期刊：
影响因子：
6.1
通讯作者：
Chida Masayuki
中科院分区：
文献类型：
--
作者：
Hayashi Keitaro;Nakazato Yoshimasa;Morito Noriaki;Sagi Mizuki;Fujita Tomoe;Anzai Naohiko;Chida Masayuki
胸腺癌是一种罕见的上皮性肿瘤，目前尚无最佳的药物治疗方法。为了开发胸腺癌的新药物治疗方法，我们研究了氟伐他汀介导的3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR）的药理抑制作用。主要方法手术切除胸腺癌组织，采用免疫组化方法检测HMGCR的表达。用氟伐他汀（1 ~ 10 μM）处理Ty82人胸腺癌细胞，观察其生长情况。关键发现shmgcr在胸腺组织癌细胞上表达，而在正常上皮细胞上不表达。氟伐他汀抑制HMGCR抑制细胞增殖，诱导Ty-82人胸腺癌细胞死亡。氟伐他汀通过阻断香叶基香叶基焦磷酸（GGPP）的产生介导其抗肿瘤作用，GGPP是一种由甲羟戊酸产生的类异戊二烯，与小GTPases结合，促进细胞增殖。意义氟伐他汀对胸腺癌有明显的抗肿瘤作用。结果表明他汀类药物在胸腺癌治疗中具有临床益处。
AimsThymic carcinoma is a rare epithelial tumor, for which, optimal pharmacotherapeutic methods have not yet been established. To develop new drug treatments for thymic carcinoma, we investigated the effects of fluvastatin-mediated pharmacological inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) on thymic carcinoma.Main methodsThymic carcinoma tissue was surgically excised and HMGCR expression was assessed by immunohistochemistry. Ty82 human thymic carcinoma cells were treated with fluvastatin (1–10 μM) and their growth was monitored.Key findingsHMGCR was expressed on carcinoma cells but not on normal epithelial cells in thymic tissue. Inhibition of HMGCR by fluvastatin suppressed cell proliferation and induced the death of Ty-82 human thymic carcinoma cells. Fluvastatin mediated its antitumor effects by blocking the production of geranylgeranyl-pyrophosphate (GGPP), an isoprenoid that is produced from mevalonate and binds to small GTPases, which promotes cell proliferation.SignificanceFluvastatin showed marked antitumor effects on thymic carcinoma. The results suggest that the statin has clinical benefits in thymic carcinoma management.