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首页> 外文期刊>Biomarker Research >Statins inhibit proliferation and cytotoxicity of a human leukemic natural killer cell line
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Statins inhibit proliferation and cytotoxicity of a human leukemic natural killer cell line

机译：他汀类药物抑制人类白血病自然杀伤细胞系的增殖和细胞毒性

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BackgroundNatural killer cells comprise the body’s first line of defense against virus-infected cells. As is true of all lymphocytes, natural killer cell malignancies can develop, however natural killer cell leukemias can be very difficult to treat due to their intrinsic resistance to chemotherapeutic agents. With the recent understanding that statin drugs may have anti-cancer properties, our investigations have focused on the ability of statins to inhibit the growth and cytotoxicity of the YT-INDY natural killer cell leukemia cell line. ResultsOur findings indicate that several statin compounds can inhibit YT-INDY proliferation disrupt cell cycle progression and abrogate natural killer cell cytotoxicity. Since natural killer cell leukemia cytotoxicity may play a role in the pulmonary damage seen in these patients, this is an important finding. Cytotoxicity, proliferation and cell cycle progression could be restored by the addition of mevalonate, signifying that the statin effects are brought about through HMG CoA reductase inhibition. The mevalonate pathway intermediate geranylgeranyl pyrophosphate, but not other intermediates in the mevalonate pathway, partially reversed statin-induced inhibition of YT-INDY proliferation and cytotoxicity. These results suggest that blockage of products made in the latter part of the mevalonate pathway may account for the observed inhibitory effects on YT-INDY proliferation and cytotoxicity. However, geranylgeranyl pyrophosphate could not reverse the statin-induced inhibition of the cell cycle. ConclusionsThese results suggest that the statin drugs should be investigated as a potential therapeutic strategy for human natural killer cell leukemias possibly in combination with chemotherapeutic agents.
机译：背景自然杀伤细胞是人体抵御病毒感染细胞的第一道防线。正如所有淋巴细胞一样，自然杀伤性细胞恶性肿瘤会发展，但是由于自然杀伤性细胞对化学治疗剂的固有抗性，因此很难治疗。随着对他汀类药物可能具有抗癌特性的最新了解，我们的研究集中在他汀类药物抑制YT-INDY天然杀伤细胞白血病细胞系生长和细胞毒性的能力上。结果我们的发现表明，几种他汀类化合物可抑制YT-INDY增殖，破坏细胞周期进程并消除自然杀伤细胞的细胞毒性。由于自然杀伤细胞白血病的细胞毒性可能在这些患者的肺损伤中起作用，因此这是一个重要发现。通过添加甲羟戊酸可以恢复细胞毒性，增殖和细胞周期进程，这表明他汀类药物的作用是通过抑制HMG CoA还原酶来实现的。甲羟戊酸途径中间体香叶基香叶基焦磷酸酯，而不是甲羟戊酸途径中的其他中间体，部分逆转了他汀类药物诱导的对YT-INDY增殖和细胞毒性的抑制作用。这些结果表明，在甲羟戊酸途径的后半部分中制备的产物的阻滞可能解释了观察到的对YT-INDY增殖和细胞毒性的抑制作用。但是，香叶基香叶基香叶基焦磷酸不能逆转他汀类药物诱导的细胞周期抑制。结论这些结果表明，应将他汀类药物作为可能与化学治疗剂联合使用的治疗人类自然杀伤细胞白血病的潜在治疗策略进行研究。

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