白藜芦醇抗顺铂耐受的恶性树突状细胞--ihDCTC的作用及其机制研究
首发时间:2017-10-23
摘要:目的:肿瘤微环境(TME)促进肿瘤细胞耐药越来越被关注,但肿瘤微环境恶性转化细胞自身的耐药情况知之甚少。本文探讨TME中被胶质瘤干细胞(GSC)诱导恶性转化细胞株(ihDCTC)对化疗药的敏感性.方法:体外,用Res和Cis对上述两种细胞进行干预,Annexin-V和Hoechest33342染色检测细胞凋亡;流式细胞术检测细胞周期分布;Western bolt测相关蛋白表达。体内,Res和Cis治疗荷ihDCTC瘤的裸小鼠,绘制肿瘤增殖曲线,取出肿瘤组织称质量、再培养、免疫组织化学染色等。结果:在体外 24h、48h、72h的IC50值,Cis处理ihDCTC分别是处理SU3的3.62倍、3.25倍、2.10倍。相比之下,Res处理ihDCTC 分别是处理SU3的IC50值的0.03倍、0.47倍、1.19倍; 体内,移植瘤的质量(g),对照、Res、Cis、Res+Cis分别为1.44±0.19,0.45±0.12,0.94±0.80,0.68±0.35。与对照组比的P值分别为0.008,0.164和0.039;移植瘤组织IL-6、p-STAT3、NF-κB蛋白表达只有Res处理组明显降低。结论:本研究证明ihDCTC相比SU3对Cis更加耐受,对Res的耐受性相当,表明肿瘤微环境诱导恶性转化的恶性树突状细胞相比肿瘤干细胞更加耐受传统化疗药物,这可能与IL-6/p-STAT3/NF-κB的调控有关。
关键词: 肿瘤干细胞 免疫炎性细胞恶性转化 肿瘤细胞耐药 白藜芦醇 顺铂?????
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Malignantly Transformed Dendritic Cell Line SU3-ihDCTC Induced by Glioma Stem Cells and Study on Its Sensitivity to Resveratrol
Abstract:Objective: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. Methods: 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. Results: At 24h, 48h and 72h, 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. Conclusion: 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. Indicated that Tumor stem cells induced tumor microenvironment immune inflammatory cells malignant transformation ,More resistant to conventional chemotherapy drugs than parent tumor stem cells.and the underlying mechanisms may be related to IL - 6 / p-STAT3 / NF-κB regulation.
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白藜芦醇抗顺铂耐受的恶性树突状细胞--ihDCTC的作用及其机制研究
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