Bie Jia Jian Pill Combined with Bone Mesenchymal Stem Cells Regulates microRNA-140 to Suppress Hepatocellular Carcinoma Stem Cells.
Bie Jia Jian Pill Combined with Bone Mesenchymal Stem Cells Regulates microRNA-140 to Suppress Hepatocellular Carcinoma Stem Cells.
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鳖甲煎丸联合骨间充质干细胞调控microRNA-140抑制肝癌干细胞
DOI：
10.15283/ijsc20157
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发表时间：
2021-08-30
影响因子：
2.3
通讯作者：
Yueqiang H
中科院分区：
文献类型：
--
作者：
Jingjing H;Hongna H;Wenfu Z;Jianlin L;Guochu H;Yuanjia L;Songlin C;Yueqiang H
具有致瘤潜能的肿瘤干细胞（cancer stem cells，CSCs）是肝细胞癌（hepatocellular carcinoma，HCC）复发和治疗耐药的关键因素。骨髓间充质干细胞（BMSCs）被证明在肝细胞的保护中发挥重要作用。鳖甲煎丸是一种治疗肝纤维化和肝癌的传统中药。本研究旨在探讨BJJP与BMSCs联合应用对肝癌细胞系的潜在作用。采用流式细胞术通过测量CD 24、CD 133、CD 44、CD 73、CD 105、CD 166、CD 29、CD 14和CD 34来鉴定从BALB/c小鼠分离的BMSC和从Huh 7细胞富集的CSC。同时测定BMSCs的分化潜能。CCK-8法和克隆形成法检测细胞活力和增殖能力。采用PCR和Western blot检测CSCs生物标志物和Wnt/β-catenin信号通路相关蛋白的表达。TOP-Flash/FOP-Flash荧光素酶法检测β-catenin/TCF活性。与未处理的CSC相比，BJJP或BMSC单独处理CSC导致miR-140表达增加和细胞凋亡，以及CD 24、CD 133、EpCAM表达和细胞活力降低。BJJP或BMSC单独处理后，发现Wnt/β-catenin信号通路相关蛋白Wnt 3a和β-catenin的表达下调。BJJP+BMSCs联合应用可进一步增强对CSCs的抑制作用。下调CSCs中miR-140的表达可部分阻断BMSCs或BMSCs+BJJP对CSCs Wnt 3a和β-catenin表达的影响以及对CSCs细胞活力和凋亡的影响。在转染miR-140过表达的CSC中发现了逆转的表达模式。综上所述，我们证明BJJP+BMSCs可以通过调节miR-140和抑制Wnt/β-catenin信号通路进一步增强对CSC的抑制作用。本研究证实了BJJP+BMSCs在肝癌治疗中的潜力。
Cancer stem cells (CSCs) with tumorigenic potential are reported as the crucial factors of hepatocellular carcinoma (HCC) recurrence and therapy resistance. Bone mesenchymal stem cells (BMSCs) are documented to play an important role in the protection of hepatocytes. Bie Jia Jian pill (BJJP), a Traditional Chinese Medicine, has been used to treat liver fibrosis and liver cancer. This study aimed to explore the potential role of combined use of BJJP with BMSCs in HCC cell lines. Flow cytometry was used to identify BMSCs isolated from BALB/c mice and CSCs enriched from Huh7 cells by measuring CD24, CD133, CD44, CD73, CD105, CD166, CD29, CD14 and CD34. Differentiation potential of BMSCs was also determined. Cell viability and proliferation ability of CSCs were determined by CCK-8 assay and clone formation assay. The expressions of CSCs biomarkers and Wnt/β-catenin signal pathway related proteins were determined by PCR and western blot. TOP-Flash/FOP-Flash luciferase assay was applied to measure the activity of β-catenin/TCF. Compared with untreated CSCs, BJJP or BMSCs treatment alone on CSCs lead to increased miR-140 expression and cell apoptosis, as well as decreased expressions of CD24, CD133, EpCAM and cell viability. Downregualted expressions of Wnt/β-catenin signal pathway related proteins, Wnt3a and β-catenin were found in response to BJJP or BMSCs treatment alone. The combination of BJJP＋BMSCs treatment on CSCs could further enhance the suppressive effect on CSCs. Down-regulation of miR-140 in CSCs partially blocked the effects of BMSCs or BMSCs＋BJJP on the expressions of Wnt3a and β-catenin as well as the cell viability and apoptosis of CSCs. Reversed expression pattern was found in CSCs transfected with miR-140 overexpression. Taken together, we demonstrate that BJJP＋BMSCs together could further enhance the suppressive effect on CSCs through regulating miR-140 and suppressing Wnt/β-catenin signal pathway. This study demonstrated the potential of BJJP＋BMSCs in therapeutic treatment of HCC.
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影响因子：
3.7
作者：
Yagi H;Kitagawa Y
通讯作者：
Kitagawa Y
影响因子：
4.2
作者：
Mahboudi, Hossein;Soleimani, Masoud;Kazemi, Bahram
通讯作者：
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影响因子：
12.4
作者：
Shao, Yingjie;Song, Xing;Jiang, Jingting
通讯作者：
Jiang, Jingting
影响因子：
5.4
作者：
Shi, Shuo;Zhang, Min;Li, Biao
通讯作者：
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影响因子：
6.4
作者：
Wu, Dawei;Zhang, Jun;Mao, Jun
通讯作者：
Mao, Jun