Inhibition of fatty acid metabolism reduces human myeloma cells proliferation.
Inhibition of fatty acid metabolism reduces human myeloma cells proliferation.
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DOI：
10.1371/journal.pone.0046484
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Perdomo G
中科院分区：
文献类型：
--
作者：
Tirado-Vélez JM;Joumady I;Sáez-Benito A;Cózar-Castellano I;Perdomo G
多发性骨髓瘤是一种以浆细胞克隆性增殖为特征的血液恶性肿瘤。有人提出，靶向癌细胞代谢将提供一种新的选择性抗癌治疗策略。在这项工作中，我们测试了抑制β-氧化和脂肪酸从头合成会减少人骨髓瘤细胞增殖的假设。我们评估了依托莫克西和奥利司他对骨髓瘤细胞中脂肪酸代谢、葡萄糖代谢、细胞周期分布、增殖、细胞死亡和G1/S期调节蛋白表达的影响。 Etomoxir 和奥利司他分别抑制骨髓瘤细胞中的β-氧化和脂肪酸从头合成，而不显着改变葡萄糖代谢。这些效应与细胞活力降低和 G0/G1 期细胞周期停滞有关。具体来说，依托莫克西和奥利司他可减少 40-70% 的骨髓瘤细胞增殖。依托莫克西和奥利司他的组合对细胞增殖产生附加抑制作用。奥利司他诱导细胞凋亡，并使 RPMI-8226 细胞对硼替佐米诱导的细胞凋亡敏感，而依托莫克西不改变细胞凋亡。最后，两种药物对细胞增殖的抑制作用与 p21 蛋白水平和视网膜母细胞瘤蛋白磷酸化水平的降低有关。总之，抑制脂肪酸代谢代表了治疗人类多发性骨髓瘤的潜在治疗方法。
Multiple myeloma is a haematological malignancy characterized by the clonal proliferation of plasma cells. It has been proposed that targeting cancer cell metabolism would provide a new selective anticancer therapeutic strategy. In this work, we tested the hypothesis that inhibition of β-oxidation and de novo fatty acid synthesis would reduce cell proliferation in human myeloma cells. We evaluated the effect of etomoxir and orlistat on fatty acid metabolism, glucose metabolism, cell cycle distribution, proliferation, cell death and expression of G1/S phase regulatory proteins in myeloma cells. Etomoxir and orlistat inhibited β-oxidation and de novo fatty acid synthesis respectively in myeloma cells, without altering significantly glucose metabolism. These effects were associated with reduced cell viability and cell cycle arrest in G0/G1. Specifically, etomoxir and orlistat reduced by 40–70% myeloma cells proliferation. The combination of etomoxir and orlistat resulted in an additive inhibitory effect on cell proliferation. Orlistat induced apoptosis and sensitized RPMI-8226 cells to apoptosis induction by bortezomib, whereas apoptosis was not altered by etomoxir. Finally, the inhibitory effect of both drugs on cell proliferation was associated with reduced p21 protein levels and phosphorylation levels of retinoblastoma protein. In conclusion, inhibition of fatty acid metabolism represents a potential therapeutic approach to treat human multiple myeloma.
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影响因子：
3.5
作者：
Manuel Tirado-Velez, Jose;Benitez-Rondan, Alicia;Perdomo, German
通讯作者：
Perdomo, German
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作者：
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作者：
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通讯作者：
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作者：
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