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经二甲基亚砜(DMSO)处理改变的Hepa1-6细胞在体内诱导抗肿瘤免疫。

Altered Hepa1-6 cells by dimethyl sulfoxide (DMSO)-treatment induce anti-tumor immunity in vivo.

作者信息

Jiang Zhengyu, Zhang Hongxia, Wang Ye, Yu Bin, Wang Chen, Liu Changcheng, Lu Juan, Chen Fei, Wang Minjun, Yu Xinlu, Lin Jiahao, Pan Xinghua, Wang Pin, Zhu Haiying

机构信息

Department of Cell Biology, Second Military Medical University, Shanghai, P.R. China.

Center for Stem Cell and Medicine, The Graduate School, Second Military Medical University, Shanghai, P.R. China.

出版信息

Oncotarget. 2016 Feb 23;7(8):9340-52. doi: 10.18632/oncotarget.7009.

Abstract

Cancer immunotherapy is the use of the immune system to treat cancer. Our current research proposed an optional strategy of activating immune system involving in cancer immunotherapy. When being treated with 2% DMSO in culture medium, Hepa1-6 cells showed depressed proliferation with no significant apoptosis or decreased viability. D-hep cells, Hepa1-6 cells treated with DMSO for 7 days, could restore to the higher proliferation rate in DMSO-free medium, but alteration of gene expression profile was irreversible. Interestingly, tumors from D-hep cells, not Hepa1-6 cells, regressed in wild-type C57BL/6 mice whereas D-hep cells exhibited similar tumorigenesis as Hep1-6 cells in immunodeficient mice. As expected, additional Hepa1-6 cells failed to form tumors in the D-hep-C57 mice in which D-hep cells were eliminated. Further research confirmed that D-hep-C57 mice established anti-tumor immunity against Hepa1-6 cells. Our research proposed viable tumor cells with altered biological features by DMSO-treatment could induce anti-tumor immunity in vivo.

摘要

癌症免疫疗法是利用免疫系统来治疗癌症。我们目前的研究提出了一种激活参与癌症免疫疗法的免疫系统的可选策略。当在培养基中用2%二甲基亚砜(DMSO)处理时,Hepa1-6细胞增殖受到抑制,且无明显凋亡或活力下降。D-hep细胞,即经DMSO处理7天的Hepa1-6细胞,在无DMSO的培养基中可恢复到较高的增殖率,但基因表达谱的改变是不可逆的。有趣的是,在野生型C57BL/6小鼠中,源自D-hep细胞而非Hepa1-6细胞的肿瘤发生消退,而在免疫缺陷小鼠中,D-hep细胞表现出与Hep1-6细胞相似的肿瘤发生情况。正如预期的那样,在已清除D-hep细胞的D-hep-C57小鼠中,额外的Hepa1-6细胞无法形成肿瘤。进一步的研究证实,D-hep-C57小鼠建立了针对Hepa1-6细胞的抗肿瘤免疫力。我们的研究表明,经DMSO处理具有改变生物学特性的存活肿瘤细胞可在体内诱导抗肿瘤免疫力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/558b/4891044/39bedc16a100/oncotarget-07-9340-g001.jpg

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