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陈敬腾, 余铃, 方硕, 郭良煜, 郭卫春. Notch信号通路可通过激活Slug调控骨肉瘤上皮-间质转化[J]. 肿瘤防治研究, 2020, 47(1): 6-12. DOI: 10.3971/j.issn.1000-8578.2020.19.0704
引用本文: 陈敬腾, 余铃, 方硕, 郭良煜, 郭卫春. Notch信号通路可通过激活Slug调控骨肉瘤上皮-间质转化[J]. 肿瘤防治研究, 2020, 47(1): 6-12. DOI: 10.3971/j.issn.1000-8578.2020.19.0704
CHEN Jingteng, YU Ling, FANG Shuo, GUO Liangyu, GUO Weichun. Notch Signaling Pathway Regulates Epithelial-mesenchymal Transition of Osteosarcoma by Activating Slug[J]. Cancer Research on Prevention and Treatment, 2020, 47(1): 6-12. DOI: 10.3971/j.issn.1000-8578.2020.19.0704
Citation: CHEN Jingteng, YU Ling, FANG Shuo, GUO Liangyu, GUO Weichun. Notch Signaling Pathway Regulates Epithelial-mesenchymal Transition of Osteosarcoma by Activating Slug[J]. Cancer Research on Prevention and Treatment, 2020, 47(1): 6-12. DOI: 10.3971/j.issn.1000-8578.2020.19.0704

Notch信号通路可通过激活Slug调控骨肉瘤上皮-间质转化

Notch Signaling Pathway Regulates Epithelial-mesenchymal Transition of Osteosarcoma by Activating Slug

  • 摘要:
    目的 探究Notch信号通路对骨肉瘤上皮-间质转化的影响及其机制。
    方法 通过慢病毒转染技术转染骨肉瘤细胞, 利用si-slug敲除Slug基因, 采用免疫荧光染色技术、Western blot、qRT-PCR、相差显微镜、划痕实验和TranswellTM实验检测相应骨肉瘤细胞形态、侵袭、转移及上皮间质转化(EMT)情况。动物实验比较各组小鼠成瘤后体积、重量变化; 采用qRT-PCR检测离体肿瘤组织中Slug和N-cadherin的表达。
    结果 成功得到Notch信号通路激活或抑制的骨肉瘤细胞, Notch信号通路激活组E-cadherin表达无明显变化, N-cadherin表达显著升高, 骨肉瘤细胞长/短轴比率上调, Slug、Twist1表达上调, 侵袭及转移能力增强。动物实验发现Notch信号通路激活可促进体内成瘤, 离体骨肉瘤组织中Slug、N-cadherin阳性率增高。Slug被成功敲除后Notch信号激活组骨肉瘤细胞形态、侵袭及转移能力发生逆转。
    结论 Notch信号通路对骨肉瘤上皮-间质转化过程具有促进作用, 其机制可能与激活Slug有关。

     

    Abstract:
    Objective To investigate the effect and mechanism of Notch signaling pathway on epithelial-mesenchymal transition (EMT) of osteosarcoma.
    Methods We used lentivirus transfection technology to transfect osteosarcoma cells, and used si-slug to knock down the Slug gene. Then we used immunofluorescence staining, Western blot, qRT-PCR, phase contrast microscopy, wound healing and TranswellTM test to detect the morphological, the invasion and metastasis and the influences of EMT of the corresponding osteosarcoma cells. In animal experiments, the volume and weight of nude mice were compared after tumorigenesis, and the expression of Slug and N-cadherin in tumor tissues were detected by qRT-PCR.
    Results We successfully obtained osteosarcoma cells with activated or inhibited Notch signaling pathway. In Notch activated group, the expression of N-cadherin was increased significantly, the ratio of long/short axis, the expression of Slug and Twist1, as well as the invasion and metastasis abilities of osteosarcoma cells were increased. Animal experiments showed that activated Notch signaling pathway could promote tumorigenesis in vivo, and the positive rates of Slug and N-cadherin in osteosarcoma tissues in xenograft were upregulated. The morphology, invasion and metastasis of osteosarcoma cells in the Notch activated group were reversed after Slug was successfully knocked out.
    Conclusion Notch signaling pathway promotes the EMT of osteosarcoma, which may be related to Slug activation.

     

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