https://scholars.lib.ntu.edu.tw/handle/123456789/473615
標題: | Targeting the CXCR4/CXCL12 axis in treating epithelial ovarian cancer | 作者: | TSUI-LIEN MAO Fan K.F. Liu C.L. |
公開日期: | 2017 | 出版社: | Nature Publishing Group | 卷: | 24 | 期: | 10 | 起(迄)頁: | 621-629 | 來源出版物: | Gene Therapy | 摘要: | Ovarian carcinoma is the most crucial and difficult target for available therapeutic treatments among gynecological malignancies, and great efforts are required to find an effective solution. Molecular studies showed that the chemokine stromal cell-derived factor-1 (also known as CXCL12) and its receptor, CXCR4, are key determinants of tumor initiation, progression and metastasis in ovarian carcinomas. Hence, it is generally believed that blocking the CXCR4/CXCL12 pathway could serve as a potential therapy for patients with ovarian cancer. Herein, we investigated the role of the CXCR4/CXCL12 axis in regulating ovarian cancer progression. Using flow cytometry, a real-Time PCR and western blot analyses, we showed that the chemokine receptor CXCR4 protein and mRNA were overexpressed in human epithelial ovarian cancer cell lines, and these were closely correlated with poor outcomes. Moreover, silencing CXCR4 by small hairpin RNA in HTB75 cells reduced cell proliferation, migration and invasion and significantly reduced RhoA and Rac-1/Cdc42 expressions, whereas overexpression of CXCR4 in SKOV3 cells significantly increased cell migration and markedly increased RhoA, Rac-1/Cdc42 levels. Silencing CXCR4 also led to decreased in vitro cytotoxicity of AMD3100, a specific antagonist of CXCR4, which exerts its effect upon CXCR4 expression. Remarkably, knockdown of CXCR4 in HTB75 cells led to a significantly decreased capability to form tumors in vivo, and the Ki67 proliferation index of xenograft tumors showed a dramatic reduction. Our results revealed that the CXCR4/CXCL12 pathway represents a promising therapeutic target for epithelial ovarian carcinoma. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85032441873&doi=10.1038%2fgt.2017.69&partnerID=40&md5=a958d52abc5e7550187a3735306a3112 https://scholars.lib.ntu.edu.tw/handle/123456789/473615 |
ISSN: | 0969-7128 | DOI: | 10.1038/gt.2017.69 | SDG/關鍵字: | chemokine receptor CXCR4; Ki 67 antigen; messenger RNA; plerixafor; protein Cdc42; Rac1 protein; RhoA guanine nucleotide binding protein; short hairpin RNA; stromal cell derived factor 1; chemokine receptor CXCR4; heterocyclic compound; Rac1 protein; RhoA guanine nucleotide binding protein; stromal cell derived factor 1; Article; cancer inhibition; cancer prognosis; Caov-3 cell line; controlled study; drug cytotoxicity; female; flow cytometry; gene overexpression; gene silencing; human; human cell; in vitro study; in vivo study; metastasis inhibition; ovary carcinoma; OVCAR-3 cell line; priority journal; real time polymerase chain reaction; SK-OV-3 cell line; TOV-112D cell line; tumor invasion; Western blotting; animal; antagonists and inhibitors; carcinoma; genetics; metabolism; mouse; nonobese diabetic mouse; ovary tumor; procedures; RNAi therapeutics; SCID mouse; tumor cell line; Animals; Carcinoma; Cell Line, Tumor; Chemokine CXCL12; Female; Heterocyclic Compounds; Humans; Mice; Mice, Inbred NOD; Mice, SCID; Ovarian Neoplasms; rac1 GTP-Binding Protein; Receptors, CXCR4; rhoA GTP-Binding Protein; RNAi Therapeutics |
顯示於: | 病理學科所 |
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