Blood:可有效抑制体内外病毒相关性淋巴瘤的新型神经酰胺类似物

2020-06-13 QQY MedSci原创

研究人员合成了一些列新的神经酰胺类似物,发现其中一些能在体内外有效的抑制KSHV+淋巴瘤的生长。

原发性渗出性淋巴瘤(PEL)是一种侵袭性的恶性肿瘤,即使在积极化疗的情况下预后也很差,通常伴随人类致癌病毒之一的卡波西肉瘤相关疱疹病毒(Kaposi's sarcoma-associated herpesvirus,KSHV)感染

目前,PEL尚无特效治疗方法,因此开发新的治疗方法具有重要意义。

鞘脂类代谢在决定肿瘤细胞命运中起着重要作用。既往研究已经证明鞘磷脂代谢与KSHV+肿瘤细胞存活有关。为了进一步开展鞘磷脂代谢靶向治疗,经过筛选了一系列新合成的神经酰胺类似物后,Chen等人筛选出了具有有效抗PEL活性的化合物。

这些化合物通过调节神经酰胺合成或神经酰胺代谢酶,诱导PEL凋亡、细胞周期阻滞和细胞内神经酰胺的产生,并在体内显著抑制肿瘤进展,且无明显毒性。这些新化合物还增加了PEL细胞中病毒裂解基因的表达。

此外,转录对比分析还揭示了这些化合物诱导PEL细胞死亡的作用机制,并鉴定了一组新的细胞基因,包括AURKA和CDCA3,受鞘脂代谢调控,对PEL存活必不可少。

这些数据为开发这种病毒相关恶性肿瘤的基于鞘磷脂代谢的靶向药物提供了框架。

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    2020-06-15 xugc
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    2020-06-13 lifefamily@163

    #Blood#血液牛刊

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