Gastroenterology:高胆固醇水平可增加自然杀伤细胞的抗肿瘤功能

2020-01-29 不详 MedSci原创

血清胆固醇水平与肝细胞癌(HCC)发展之间的关系仍然令人困惑。因此本项研究旨在探究血清胆固醇水平对小鼠肝肿瘤发展的影响。

背景与目的
血清胆固醇水平与肝细胞癌(HCC)发展之间的关系仍然令人困惑。因此本项研究旨在探究血清胆固醇水平对小鼠肝肿瘤发展的影响。

方法
研究人员对C57BL / 6J小鼠,低密度脂蛋白受体基因受到破坏的小鼠(Ldlr -/-小鼠)和有条件删除自然杀伤(NK)细胞的小鼠(NK dele小鼠)进行了对照研究。研究人员给一些C57BL / 6J和NK dele小鼠注射二乙基二十二胺(DEN)以诱导肝肿瘤形成。将小鼠置于正常饮食(ND)或高胆固醇饮食(HCD)(诱导高血清胆固醇水平)。同时研究人员还研究了纯合破坏ApoE的小鼠(ApoE -/-小鼠),它们会自发形成高血清胆固醇。C57BL / 6J和NK dele在ND或HCD的小鼠植入Hep1-6(小鼠肝癌)细胞,并监测异种移植肿瘤的生长和肺转移。最后研究人员收集肝脏和肿瘤组织并通过组织学免疫组织化学和RNA-seq分析进行分析。从小鼠中分离出NK细胞,并分析其胆固醇含量,脂质筏形成,免疫信号传导和功能变化。

结果
与ND小鼠相比,DEN注射或Hep1-6细胞植入后,具有高血清胆固醇水平的HCD和ApoE -/-小鼠的C57BL / 6J小鼠出现更少、更小的肝肿瘤和肺转移。与来自ND喂养的小鼠的肿瘤相比,来自HCD喂养的小鼠和ApoE -/-小鼠的肝肿瘤的NK细胞数量增加。与ND小鼠NK细胞相比,从用HCD喂养的C57BL / 6J小鼠中分离到的NK细胞具有更高的NK细胞激活受体(NCR1和NKG2D),效应子功能标记(粒酶B和穿孔素)以及细胞因子和趋化因子的表达。这些NK细胞还具有增强的针对小鼠肝癌细胞的细胞毒性活性,胆固醇积累,脂质筏形成增加和免疫信号激活。血清胆固醇水平与从人肝癌分离的NK细胞的数量和活性有关。

结论
由于HCD或ApoE的基因破坏,血清胆固醇水平升高的小鼠在注射肝癌细胞或化学致癌物后出现的肿瘤越来越小。

原始出处:

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    2020-04-30 许安
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