Human amniotic mesenchymal stem cells inhibit hepatocellular carcinoma in tumour-bearing mice.
Human amniotic mesenchymal stem cells inhibit hepatocellular carcinoma in tumour-bearing mice.
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人羊膜间充质干细胞抑制荷瘤小鼠的肝细胞癌
DOI：
10.1111/jcmm.15668
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发表时间：
2020-09
影响因子：
5.3
通讯作者：
Xin HB
中科院分区：
文献类型：
--
作者：
Liu QW;Li JY;Zhang XC;Liu Y;Liu QY;Xiao L;Zhang WJ;Wu HY;Deng KY;Xin HB
肝细胞癌（HCC）是世界上第三大癌症相关死亡原因。人羊膜间充质干细胞（human amniotic mesenchymal stem cells，hAMSCs）具有多能性、低免疫原性和无致瘤性等特点。特别是，hAMSC的免疫抑制和抗炎作用使其适用于治疗HCC。在这里，我们报道了静脉注射hAMSC通过抑制Hepg 2细胞荷瘤小鼠的细胞增殖和诱导细胞凋亡来显著抑制HCC。使用GFP标记的hAMSC的细胞追踪实验表明，干细胞具有迁移到肿瘤发生部位以抑制肿瘤生长的能力。重要的是，hAMSC和条件培养基（hAMSC-CM）在体外具有相似的抗肿瘤作用，表明hAMSC衍生的细胞因子可能参与其抗肿瘤作用。抗体芯片检测显示hAMSC高表达dickkopf-3（DKK-3）、dickkopf-1（DKK-1）和胰岛素样生长因子结合蛋白3（IGFBP-3）。此外，通过在体外应用DKK-3、DKK-1和IGFBP-3的抗体或特异性siRNA，进一步证实了hAMSC的抗肿瘤作用。在机制上，hAMSCs来源的DKK-3、DKK-1和IGFBP-3分别通过抑制Wnt/β-catenin信号通路和IGF-1 R介导的PI 3 K/AKT信号通路，显著抑制Hepg 2细胞增殖，促进细胞凋亡。综上所述，我们的研究表明，hAMSCs具有显着的抗肿瘤作用，在体内和体外，并可能为肝癌的临床治疗提供一种新的策略。
Hepatocellular carcinoma (HCC) is the third leading cause of the cancer‐related death in the world. Human amniotic mesenchymal stem cells (hAMSCs) have been characterized with a pluripotency, low immunogenicity and no tumorigenicity. Especially, the immunosuppressive and anti‐inflammatory effects of hAMSCs make them suitable for treating HCC. Here, we reported that hAMSCs administrated by intravenous injection significantly inhibited HCC through suppressing cell proliferation and inducing cell apoptosis in tumour‐bearing mice with Hepg2 cells. Cell tracking experiments with GFP‐labelled hAMSCs showed that the stem cells possessed the ability of migrating to the tumorigenic sites for suppressing tumour growth. Importantly, both hAMSCs and the conditional media (hAMSC‐CM) have the similar antitumour effects in vitro, suggesting that hAMSCs‐derived cytokines might be involved in their antitumour effects. Antibody array assay showed that hAMSCs highly expressed dickkopf‐3 (DKK‐3), dickkopf‐1 (DKK‐1) and insulin‐like growth factor‐binding protein 3 (IGFBP‐3). Furthermore, the antitumour effects of hAMSCs were further confirmed by applications of the antibodies or the specific siRNAs of DKK‐3, DKK‐1 and IGFBP‐3 in vitro. Mechanically, hAMSCs‐derived DKK‐3, DKK‐1 and IGFBP‐3 markedly inhibited cell proliferation and promoted apoptosis of Hepg2 cells through suppressing the Wnt/β‐catenin signalling pathway and IGF‐1R‐mediated PI3K/AKT signalling pathway, respectively. Taken together, our study demonstrated that hAMSCs possess significant antitumour effects in vivo and in vitro and might provide a novel strategy for HCC treatment clinically.
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影响因子：
11.8
作者：
Krishnamurthy N;Kurzrock R
通讯作者：
Kurzrock R
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影响因子：
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影响因子：
7.5
作者：
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通讯作者：
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影响因子：
4.5
作者：
Lee, Wayne Y. W.;Zhang, Ting;Li, Gang
通讯作者：
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影响因子：
12.4
作者：
Ahmed, Atique U.;Rolle, Cleo E.;Lesniak, Maciej S.
通讯作者：
Lesniak, Maciej S.