Targeting the CXCR4/CXCL12 axis in treating epithelial ovarian cancer

T. L. Mao, K. F. Fan, C. L. Liu

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)621-629
Number of pages9
JournalGene Therapy
Volume24
Issue number10
DOIs
Publication statusPublished - Oct 1 2017

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Carcinoma
Ovarian Neoplasms
Cell Movement
Neoplasms
CXCR4 Receptors
Chemokine CXCL12
Chemokine Receptors
Therapeutics
Chemokines
Heterografts
Small Interfering RNA
Real-Time Polymerase Chain Reaction
Flow Cytometry
Western Blotting
Cell Proliferation
Neoplasm Metastasis
Cell Line
Messenger RNA
Ovarian epithelial cancer
Proteins

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Targeting the CXCR4/CXCL12 axis in treating epithelial ovarian cancer. / Mao, T. L.; Fan, K. F.; Liu, C. L.

In: Gene Therapy, Vol. 24, No. 10, 01.10.2017, p. 621-629.

Research output: Contribution to journalArticle

Mao, T. L. ; Fan, K. F. ; Liu, C. L. / Targeting the CXCR4/CXCL12 axis in treating epithelial ovarian cancer. In: Gene Therapy. 2017 ; Vol. 24, No. 10. pp. 621-629.
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