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Downregulation of GPR4 and TCF7 Promotes Apoptosis and Inhibits Growth and Invasion of Ovarian Cancer Cells

[ Vol. 21 , Issue. 12 ]

Author(s):

Zhuanli Bai, YinYing Wu, Yanli Yan, Shuheng Bai, Haojing Kang, Wen Ma, Jiangzhou Zhang, Ying Gao, Beina Hui, Hailin Ma, Rong Li, Xiaozhi Zhang and Juan Ren*   Pages 1544 - 1550 ( 7 )

Abstract:


Background: G protein-coupled receptor 4 (GPR4) has been reported to play an essential role in regulating the proliferation, migration and angiogenesis of vascular endothelial cells. GPR4 is also suggested play roles in the growth and angiogenesis of ovarian cancer.

Objective: To explore the function of GPR4 and transcription factor 7 (TCF7) in ovarian cancer.

Methods: The expression levels of genes involved in Wnt signaling were validated by quantitative real-time-PCR (q-RT-PCR). The effects of GPR4 and TCF7 on ovarian cancer cell invasion and apoptosis were determined using soft agar, Transwell assay and flow cytometric assay. Protein levels of beta-catenin, MMP-2 and MMP-9 were evaluated by Western blotting.

Results: In this study, we found that GPR4 and TCF7 had the capacity to control cell division by altering cell cycle distribution, anchorage-independent growth, and directional cell motility of ovarian cancer cell, A2780. Also, we showed that knockdown of GPR4 and TCF7 in ovarian cancer cells A2780 induced significantly decreased cell growth and decreased invasion, as well as increased apoptosis. Down-regulation of TCF7 resulted in the decreased MMP-2 and MMP-9 level.

Conclusion: The results implicate that GPR4 behaves like an oncogene and may function through WNT pathway molecule, TCF7. Downregulation of GPR4 and TCF7 essentially inhibited cell growth and invasion and enhanced apoptosis of ovarian cancer cells, which may lay the foundation of ovarian cancer treatment.

Keywords:

GPR4, TCF7, ovarian cancer, WNT pathway, apoptosis, qRT-PCR.

Affiliation:

Department of Plastic and Aesthetic Maxillofacial Surgery, First Affiliated Hospital of Xi'an Jiao Tong University, Xi’an, Shaanxi Province, Department of Chemotherapy, Oncology Department, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, Department of Radiotherapy, Oncology Department, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, Department of Radiotherapy, Oncology Department, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, Department of Radiotherapy, Oncology Department, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, Medical School, Xi’an Jiaotong University Xi’an, Shaanxi Province, Medical School, Xi’an Jiaotong University Xi’an, Shaanxi Province, Department of Radiotherapy, Oncology Department, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, Department of Radiotherapy, Oncology Department, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, Department of Radiotherapy, Oncology Department, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, Department of Radiotherapy, Oncology Department, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, Department of Radiotherapy, Oncology Department, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, Department of Radiotherapy, Oncology Department, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province



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