Extracellular ubiquitin inhibits the apoptosis of hepatoma cells via the involvement of macrophages.

Extracellular ubiquitin inhibits the apoptosis of hepatoma cells via the involvement of macrophages.
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细胞外泛素通过巨噬细胞参与抑制肝癌细胞凋亡

DOI:
10.21037/tcr.2020.03.12
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发表时间:
2020-04
影响因子:
0.9
通讯作者:
Xia R
Xia R
中科院分区:
医学4区
文献类型:
--
作者:
Cai J;Qian X;Qi Q;Han J;Zhu X;Zhang Q;Xia R

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输血是癌症患者的重要治疗方法,但一些研究证明输血与癌症复发风险之间存在关联。储存时间影响红细胞(RBC)的质量,输注老化RBC可导致肝细胞癌(HCC)复发,这可能与老化RBC释放的泛素(Ub)有关。本研究探讨了eUb对肝癌细胞生物学特性的影响。采用CCK-8法、集落形成实验、流式细胞术和Western blot检测肝癌细胞株MHCC-97 H和HepG2.2.15的增殖和凋亡。THP-1衍生的巨噬细胞用于本研究中,并且用Transwell插入物启动肝癌细胞与巨噬细胞的共培养。我们还通过ELISA检测了巨噬细胞的分泌。eUb对肝癌细胞的增殖和凋亡无直接影响。而eUb预处理的巨噬细胞与肝癌细胞共培养后,肝癌细胞Akt/mTOR信号通路被激活,肝癌细胞凋亡明显受到抑制。此外,我们证实了eUb调节巨噬细胞的表型和分泌功能。细胞外Ub通过巨噬细胞的参与抑制肝癌细胞的凋亡,影响肿瘤局部微环境,发挥促肿瘤作用。
Blood transfusion is a vital treatment for cancer patients, but some studies have proved that there is an association between transfusion and the risk of cancer recurrence. Storage time influences the quality of red blood cells (RBCs), and the transfusion of aged RBCs can result in hepatocellular carcinoma (HCC) recurrence, which could be related to the ubiquitin (Ub) released by aged RBCs. In this study, we explored the effect of eUb on the biological characteristics of hepatoma cells. We checked the proliferation and apoptosis of hepatoma cells (MHCC-97H and HepG2.2.15) by CCK-8, colony formation assay, flow cytometry and Western blot. THP-1-derived macrophages were used in this study, and the co-culturing of hepatoma cells with macrophages was initiated with Transwell inserts. We also measured the secretion of macrophages through ELISA. eUb did not directly influence the proliferation and apoptosis of hepatoma cells. However, the Akt/mTOR signaling pathway in hepatoma cells was activated, and the apoptosis of hepatoma cells was inhibited significantly after they were co-cultured with the macrophages pretreated with eUb. In addition, we confirmed that eUb modulated the phenotype and secretion function of macrophages. Extracellular Ub repressed the apoptosis of hepatoma cells via the involvement of macrophages, which might affect the local tumor microenvironment and display pro-tumor effect.
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