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Notch2 的高表达驱动舌鳞状细胞癌的发生。

High expression of Notch2 drives tongue squamous cell carcinoma carcinogenesis.

机构信息

Department of Preventive Dentistry, Affiliated Stomatological Hospital, Fujian Medical University, 246 Yang Qiao Middle Road, Fuzhou, 350000, China; Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, 1 Xue Yuan Road, University Town, Fuzhou, 350122, China; Fujian Key Laboratory of Oral Disease, School and Hospital of Stomatology, Fujian Medical University, 88 Jiaotong Rd, Fuzhou, 350004, China.

Department of Oral and Maxillofacial Surgery, Affiliated First Hospital of Fujian Medical University, 20 Cha Zhong Road, Fuzhou, 350000, China.

出版信息

Exp Cell Res. 2021 Feb 1;399(1):112452. doi: 10.1016/j.yexcr.2020.112452. Epub 2020 Dec 28.

DOI:10.1016/j.yexcr.2020.112452
PMID:33382997
Abstract

Tongue squamous cell carcinoma (TSCC) is one of the most common cancers in the oral cavity. Notch signaling is frequently dysregulated in cancer. However, the role of Notch2 in TSCC is not well understood. The aim of this study was to investigate the effect of abnormal expression of Notch2 in TSCC. The expression of Notch2 was tested in 47 pairs of tissues from tongue cancer and normal samples by using immunohistochemical staining. Tongue cancer cells were transfected with siRNA or plasmid. The proliferation of the cells was tested by the CCK8 assay and colony formation assay. Subcutaneous tumor model was established to observe tumor growth. Transwell assay was used to detect the changes of cell migration and invasion ability. A humanized anti-Notch2 antibody was used to TSCC cells. We found that Notch2 was upregulated in tongue carcinoma tissues. Knocking down the expression of Notch2 by siRNA in the TSCC cell lines decreased proliferation ability both in vitro and in vivo. In addition, migration and invasion abilities were inhibited by knockdown of Notch2 in the TSCC cells. However, overexpression of Notch2 increased tongue cancer cell proliferation, invasion and migration. The humanized anti-Notch2 antibody inhibited TSCC cell growth. The results indicated that Notch2 is an oncogene in tongue squamous cell carcinoma and may become the target of a new approach for treating TSCC.

摘要

舌鳞状细胞癌(TSCC)是口腔最常见的癌症之一。 Notch 信号通路在癌症中经常失调。然而,Notch2 在 TSCC 中的作用尚不清楚。本研究旨在探讨 Notch2 异常表达在 TSCC 中的作用。通过免疫组织化学染色检测 47 对舌癌和正常组织中 Notch2 的表达。用 siRNA 或质粒转染舌癌细胞。用 CCK8 法和集落形成实验检测细胞增殖。建立皮下肿瘤模型观察肿瘤生长。用 Transwell 实验检测细胞迁移和侵袭能力的变化。用人源化抗 Notch2 抗体处理 TSCC 细胞。我们发现 Notch2 在舌癌组织中上调。在 TSCC 细胞系中用 siRNA 敲低 Notch2 的表达,无论是在体外还是体内,均降低了增殖能力。此外, Notch2 的敲低抑制了 TSCC 细胞的迁移和侵袭能力。然而, Notch2 的过表达增加了舌癌细胞的增殖、侵袭和迁移。人源化抗 Notch2 抗体抑制了 TSCC 细胞的生长。结果表明, Notch2 是舌鳞状细胞癌中的癌基因,可能成为治疗 TSCC 的新方法的靶点。

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