Zhang Jia, Shu Yi, Zhang Hongyang, Jiang Tingting, Gong Maoyuan, Zhu Dan, Wang Haobiao, Zou Lin
Center for Clinical Molecular Medicine, Children's Hospital, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing 400014, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2020 May 30;40(5):654-660. doi: 10.12122/j.issn.1673-4254.2020.05.07.
To investigate the effect of β-arrestin1 overexpression on tumor progression in a NCG mouse model bearing T-cell acute lymphocytic leukemia (T-ALL) Molt-4 cell xenograft.
Molt-4 cells were tagged with firefly-luciferase (F-Luc) by lentiviral infection, and fluorescence intensity of the cells was detected using a luminescence detector. Molt-4 cell lines with β-arrestin1 overexpression or knockdown were constructed by lentivirus infection and injected the tail vein in sub-lethal irradiated NCG mice. Body weight changes and survival time of the xenografted mice were observed, and the progression of T-ALL in the mice was evaluated using an fluorescence imaging system. Sixteen days after xenografting, the mice were euthanatized and tumor cell infiltration was observed in the slices of the liver and spleen.
We successfully tagged Molt-4 cells with F-Luc and overexpressed or knocked down β-arrestin1 in the tagged cells. Bioluminescent imaging showed obvious luminescence catalyzed by F-Luc in Molt-4 cells. After injection of Molt-4-Luc cells into irradiated NCG mice, a gradual enhancement of luminescence in the xenografted mice was observed over time, while the body weight of the mice decreased. Compared with the control mice, the mice xenografted with β-arrestin1-overexpressing Molt-4 cells had significantly prolonged survival time ( < 0.001), while the survival time of the mice xenografted with Molt-4 cells with β- arrestin1 knockdown was significantly shortened ( < 0.001). Histological examination revealed fewer infiltrating tumor cells in the liver and spleen of the mice xenografted with β-arrestin1-overexpressing Molt-4 cells in comparison with the mice bearing parental Molt-4 cell xenografts.
β-arrestin1 overexpression suppresses tumor progression in mice bearing Molt-4 cell xenograft.
研究β-抑制蛋白1过表达对携带T细胞急性淋巴细胞白血病（T-ALL）Molt-4细胞异种移植的NCG小鼠模型肿瘤进展的影响。
通过慢病毒感染用萤火虫荧光素酶（F-Luc）标记Molt-4细胞，并用发光检测仪检测细胞的荧光强度。通过慢病毒感染构建β-抑制蛋白1过表达或敲低的Molt-4细胞系，并将其注射到经亚致死剂量照射的NCG小鼠尾静脉中。观察异种移植小鼠的体重变化和生存时间，并用荧光成像系统评估小鼠体内T-ALL的进展。异种移植16天后，对小鼠实施安乐死，观察肝脏和脾脏切片中的肿瘤细胞浸润情况。
我们成功用F-Luc标记了Molt-4细胞，并在标记的细胞中过表达或敲低了β-抑制蛋白1。生物发光成像显示Molt-4细胞中F-Luc催化产生明显的发光。将Molt-4-Luc细胞注射到经照射的NCG小鼠体内后，随着时间的推移，异种移植小鼠体内的发光逐渐增强，而小鼠体重下降。与对照小鼠相比，异种移植β-抑制蛋白1过表达的Molt-4细胞的小鼠生存时间显著延长（<0.001），而异种移植β-抑制蛋白1敲低的Molt-4细胞的小鼠生存时间显著缩短（<0.001）。组织学检查显示，与携带亲本Molt-4细胞异种移植的小鼠相比，异种移植β-抑制蛋白1过表达的Molt-4细胞的小鼠肝脏和脾脏中浸润的肿瘤细胞较少。
β-抑制蛋白1过表达可抑制携带Molt-4细胞异种移植小鼠的肿瘤进展。
