目的 探究经普鲁士蓝纳米颗粒(prussianblue nanoparticles,PBNPs)处理的小鼠急性髓系白血病(acute myeloid leukemia,AML)细胞系WEHI-3所制备的疫苗,对AML皮下瘤生长的拮抗作用,为PBNPs用于AML免疫治疗研究提供新策略。方法 用无血清培养基(serum free medium,SFM)和PBNPs处理WEHI-3细胞,观察细胞形态的改变,并检测干性相关基因的表达;用PBNPs处理过的1×106个WEHI-3细胞反复冻融法制备AML细胞疫苗,免疫BALB/c小鼠3次10 d后,再用1×105个WEHI-3细胞攻击免疫鼠,观察不同处理疫苗免疫鼠皮下瘤生长状况。结果 SFM处理WEHI-3细胞14 d后和PBNPs处理WEHI-3细胞3 d后,细胞悬浮成团,干性相关基因的表达上调;PBNPs处理的WEHI-3细胞疫苗免疫鼠,与其他对照组相比,生存期更长、皮下瘤块更小。结论 PBNPs处理的WEHI-3细胞系可以诱导其发生干细胞样变化,用其制备的细胞疫苗免疫鼠,具有拮抗AML皮下瘤生长效应。
Abstract
OBJECTIVE To investigate anti-tumor effect of vaccine prepared from WEHI-3 cells treated with prussianblue nanoparticles(PBNPs) and provide new strategy for the study of PBNPs in acute myeloid leukemia(AML) immunotherapy. METHODS WEHI-3 cells were treated with serum free medium(SFM) and PBNPs, then the morphological changes were observed and the expression of stemness-related genes were detected. Meanwhile, tumor vaccine, prepared by repeated freezing and thawing of 1×106 PBNPs-treated WEHI-3 cells, was used to immunize BALB/c mice for three times. Ten days after the last immunization, the mice were hypodermically injected with 1×105 WEHI-3 cells and its tumor size were recorded. RESULTS WEHI-3 cells formed cellular suspension clusters after being treated with SFM for 14 days and PBNPs for 3 days, and stemness-related genes were up-regulated both in mRNA and protein levels. The mice immunized by PBNPs-treated vaccine had longer survival and smaller tumor size compared with the controls. CONCLUSION PBNPs can induce stem-like characteristic changes in WEHI-3 cell line. Vaccine prepared from PBNPs-treated WEHI-3 cells has antagonistic effect on tumor growth.
关键词
急性髓系白血病 /
普鲁士蓝纳米颗粒 /
WEHI-3细胞系 /
疫苗 /
抗急性髓系白血病效应
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Key words
acute myeloid leukemia /
prussianblue nanoparticle /
WEHI-3 /
vaccine /
antitumor effect
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中图分类号：
R967
R733.3
R392.5
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参考文献
[1] DACARRO G, TAGLIETTI A, PALLAVICINI P. Prussian blue nanoparticles as a versatile photothermal tool[J]. Molecules, 2018, 23(6): 1414.Doi: 10.3390/molecules23061414.
[2] BUSQUETS MA, ESTELRICH J. Prussian blue nanoparticles: synthesis, surface modification, and biomedical applications[J]. Drug Discov Today, 2020, 25(8): 1431-1443.
[3] BAI H Y, SUN Q H, KONG F, et al. Zwitterion-functionalized hollow mesoporous prussian blue nanoparticles for targeted and synergetic chemo-photothermal treatment of acute myeloid leukemia[J].J Mater Chem B, 2021,9(26): 5245-5254.
[4] BAO X Y, ZHENG D F, MEI F. The impact of IONPsand PBNPsnanoparticles in regulating stemness of ovarian carcinoma cells[J]. Chin Pharm J (中国药学杂志),2020, 55(11): 913-918.
[5] DOU J.Vaccine Engineering(疫苗工程学)[M]. Vol 3. Nanjing: Southeast University Press. 2020: 331-359.
[6] DOU J, LI Y, ZHAO F, et al. Identification of tumor stem-like cells in a mouse myeloma cell line[J]. Cell Mol Biol, 2009, 5(55): 1151-1160.
[7] PENG T. Persistent stemnesss of hESCs and notch1 expression changes in a self-made serum-free medium[D]. Nanchang: Nanchang University, 2014.
[8] YOSHIDA K, NAKASHIMA A, DOI S, et al. Serum-free medium enhances the immunosuppressive and antifibrotic abilities of mesenchymal stem cells utilized in experimental renal fibrosis[J]. Stem Cells Transl Med, 2018, 7(12):893-905.
[9] MARCATO P, DEAN CA, GIACOMANTONIO CA, et al. Aldehyde dehydrogenase: its role as a cancer stem cell marker comes down to the specific isoform[J]. Cell Cycle, 2011, 10(9): 1378-1384.
[10] AGRAWALP, REYNOLDSJ, CHEWS, et al. DEPTOR is a stemness factor that regulates pluripotency of embryonic stem cells[J].J Biol Chem, 2014, 289(46): 31818-31826.
[11] JORGOVANOVIC D, SONG M, WANG L, et al. Roles of IFN-γ in tumor progression and regression: a review[J]. Biomark Res, 2020, 29(8):49. Doi: 10.1186/s40364-020-00228-x.
[12] ZHAO F, DOU J, WANG J, et al. Investigation on the anti-tumor efficacy by expression of GPI-anchored mIL-21 on the surface of B16F10 cells in C57BL/6 mice[J]. Immunobiology, 2010, 215(2):89-100.
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脚注
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基金
国家重点研发计划项目资助(2017YFA0205502)
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