Antitumor effect of IL-12 gene-modified bone marrow mesenchymal stem cells combined with Fuzheng Yiliu decoction in an in vivo glioma nude mouse model

被引:10
作者
Wu, Jianjun [1 ,2 ,3 ]
Xie, Shoupin [4 ]
Li, Hailong [1 ,3 ]
Zhang, Yanxia [2 ,3 ]
Yue, Jia [1 ,3 ]
Yan, Chunlu [2 ,5 ]
Liu, Kai [2 ,5 ]
Liu, Yongqi [2 ,6 ]
Xu, Rui [1 ,2 ]
Zheng, Guisen [1 ,3 ]
机构
[1] Gansu Univ Chinese Med, Sch Publ Hlth, Lanzhou 730000, Gansu, Peoples R China
[2] Key Lab Dunhuang Med & Transformat & Prov & Minis, Lanzhou 730000, Gansu, Peoples R China
[3] Prov Key Lab Chinese Med Prevent & Control Chron, Lanzhou 730000, Gansu, Peoples R China
[4] First Peoples Hosp Lanzhou City, Dept Neurol, Lanzhou 730050, Peoples R China
[5] Gansu Univ Chinese Med, Sch Integrated Chinese & Western Med, Lanzhou 730000, Gansu, Peoples R China
[6] Gansu Univ Chinese Med, Sch Basic Med, Lanzhou 730000, Gansu, Peoples R China
关键词
Bone marrow mesenchymal stem cell; Glioma; IL-12; Fuzheng Yiliu decoction; STROMAL CELLS; MALIGNANT-TRANSFORMATION; CANCER CELLS; IFN-GAMMA; EXPRESSION; APOPTOSIS; DELIVERY; MODULATION; THERAPY; MURINE;
D O I
10.1186/s12967-021-02809-2
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Background Glioma is a complex cancer with a high morbidity and high mortality. Bone marrow mesenchymal stem cells (BMSCs) have shown promise as an excellent cell/drug delivery vehicle for gene-targeted therapy; however, maintaining genetic stability and biological activity remains difficult. Furthermore, whether BMSCs support or inhibit tumor growth remains debated. This study investigated whether a traditional Chinese medicine fomular, Fuzheng Yiliu decoction (FYD) had a synergistic antitumor effect with IL-12 gene-modified BMSCs in glioma-bearing nude mice Methods The lentivirus-mediated IL-12 gene was transfected into primarily cultured BMSCs. A total of 72 BALB/c nude mice were used to establish xenograft models with glioma U251 cells and were divided into groups (n = 12) including blank control group, nude mouse model group (model group), lentiviral transfection of BMSC group with no gene loading (BMSC group), IL-12 lentivirus-transfected BMSC group (IL-12 + BMSC group), FYD treatment group (FYD group), and FYD treatment in IL-12 lentivirus-transfected BMSC group (FYD + IL-12 + BMSC group).. After treatment for 14 days, all mice were sacrificed to collect tumor tissue and serum for more detection, such as distribution of BMSCs, cell apoptosis in xenograft tumors, serum IL-12 and INF-gamma levels, mouse weight and tumor volume were measured Results There were significantly more apoptotic cells in tumor tissue in IL-12 gene transfected group, FYD treatment group and FYD combining with IL-12 gene transfected group than that in the model group (P < 0.05). The FYD + IL-12 + BMSC group showed significantly higher Bax and lower Bcl-2 expression (P < 0.05), and serum IL-12 and INF-gamma levels (P < 0.05) were higher than that in all other groups. After the intervention, this group also showed a strong inhibitory effect against tumor growth (P < 0.05) Conclusions This study suggested FYD treatment combined with IL-12 gene-modified BMSCs shows synergistic antitumor effect in glioma-bearing nude mice.
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页数:14
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