Establishment of malignantly transformed dendritic cell line SU3-ihDCTC induced by Glioma stem cells and study on its sensitivity to resveratrol.
Establishment of malignantly transformed dendritic cell line SU3-ihDCTC induced by Glioma stem cells and study on its sensitivity to resveratrol.
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胶质瘤干细胞诱导恶性转化树突状细胞系SU3-ihDCTC的建立及其对白藜芦醇敏感性的研究
DOI：
10.1186/s12865-018-0246-z
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发表时间：
2018-02-02
期刊：
影响因子：
3
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Fei X;Wang A;Wang D;Meng X;Ma J;Hong L;Qin R;Wang A;Dong J;Huang Q;Wang Z
肿瘤微环境（TME）作为肿瘤细胞耐药的一个重要因素，正日益受到人们的重视。然而，TME中恶性转化细胞的耐药性很少被揭示。本研究旨在探讨胶质瘤干细胞（GSCs）诱导的恶性转化细胞系（ihDCTC）对化疗药物的敏感性。(1)ihDCTC细胞系的建立：采用增强型绿色荧光蛋白（EGFP）转基因裸鼠骨髓细胞体外培养树突状细胞（DCs），将其与转红色荧光蛋白（RFP）基因的GSCs（SU 3）共培养，获得ihDCTC。（2）用Res和Cis干预searcher诱导的细胞系的体外生长，通过半数抑制浓度（IC 50）、肿瘤质量和免疫组化方法评价其药物敏感性和关键信号蛋白的变化。(1)ihDCTC可表达CD 11 c和CD 80，具有永生化潜能，染色体异倍体，裸鼠体内致瘤性高。(2)在24 h、48 h和72 h，Cis处理的ihDCTC的IC 50值分别是SU 3的3.62、3.25和2.10倍，Res处理的ihDCTC的IC 50值分别是SU 3的0.03、0.47和1.19倍;（3）对照组、Res组、Cis组和Res + Cis组的体内移植瘤质量（g）分别为1.44 ± 0.19、0.45 ± 0.12、0.94 ± 0.80和0.68 ± 0.35（x ± s）。仅在Res治疗组中，异种移植组织中的IL-6、p-STAT 3和NF-κB蛋白的表达水平显著降低。体外与GSC共培养可诱导骨髓来源的树突状细胞发生恶性转化，一方面ihDCTC对传统化疗药物Cis的耐药性高于GSC，另一方面ihDCTC对Res的敏感性高于GSC。因此，本研究不仅为进一步研究TME与肿瘤耐药的相关性提供了更广阔的视野，也为探索Res的抗癌价值提供了新的思路。
As a factor contributing to the tumor cell drug resistance, tumor microenvironment (TME) is being paid increasingly attention. However, the drug resistance of malignantly transformed cells in TME has rarely been revealed. This paper is designed to investigate the sensitivity of malignantly transformed cell line (ihDCTC) induced by glioma stem cells (GSCs) in TME to chemotherapeutic drugs. (1) Establishment of ihDCTC cell line,The bone marrow cells from enhanced green fluorescent protein (EGFP) transgenic nude mice were employed to culture the dendritic cells (DCs) in vitro, which were then co-cultured with red fluorescence protein (RFP) transgenic GSCs (SU3) to obtain ihDCTC (2) Res and Cis were used to intervene in the growth of abovemetioned cell lines in vitro and Res treated in bearing ihDCTC tumor mice, followed by evaluating their drug sensitivity and changes in key signaling proteins via half maximal inhibitory concentration (IC50), tumor mass and immunostaining method. (1) ihDCTC could express CD11c and CD80 as well as possessed immortalized potential, heteroploid chromosomes and high tumorigenicity in nude mice in vivo. (2) At 24 h, 48 h and 72 h, the IC50 value of ihDCTC treated with Cis was 3.62, 3.25 and 2.10 times higher than that of SU3, while the IC50 value of ihDCTC treated with Res was 0.03, 0.47 and 1.19 times as much as that of SU3; (3) The xenograft mass (g) in vivo in the control, Res, Cis and Res + Cis groups were 1.44 ± 0.19, 0.45 ± 0.12, 0.94 ± 0.80 and 0.68 ± 0.35(x ± s) respectively. The expression levels of IL-6, p-STAT3 and NF-κB proteins in the xenograft tissue were significantly reduced only in the Res treatment group. In vitro co-culture with GSC can induce the malignant transformation of bone marrow derived dendritic cells, on the one hand, ihDCTC shows higher drug resistance to the traditional chemotherapeutic drug Cis than GSCs, but, on the other hand, appears to be more sensitive to Res than GSCs. Therefore, our findings provide a broader vision not only for the further study on the correlation between TME and tumor drug resistance but also for the exploration of Res anti-cancer value.
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影响因子：
3.4
作者：
Sato H;Wu Y;Kato Y;Liu Q;Hirai H;Yoshizawa T;Morohashi S;Watanabe J;Kijima H
通讯作者：
Kijima H
影响因子：
50.3
作者：
Hanahan, Douglas;Coussens, Lisa M.
通讯作者：
Coussens, Lisa M.
影响因子：
6.1
作者：
Castino, Roberta;Pucer, Anja;Isidoro, Ciro
通讯作者：
Isidoro, Ciro
影响因子：
5.2
作者：
Singh, Narendra P.;Singh, Udai P.;Nagarkatti, Prakash S.
通讯作者：
Nagarkatti, Prakash S.
影响因子：
2.8
作者：
Chang, Hong-Tai;Chou, Chiang-Ting;Jan, Chung-Ren
通讯作者：
Jan, Chung-Ren