ZFP403, a novel tumor suppressor, inhibits the proliferation and metastasis in ovarian cancer

Abstract

Objective: Zinc finger protein 403 (ZFP403) is located on human chromosome 17q12-21, the most common loss of heterozygosity regions for some oncogenes. However, the biological function of ZFP403 on tumor is controversial and its role in ovarian cancer remains unknown. This study aimed to investigate its biological function in ovarian cancer.

Methods: qRT-PCR and western blotting were first performed to detect the expression level of ZFP403 in ovarian cancer tissues and cells, respectively. The effect of ZFP403 on cell proliferation was determined by colony formation assays. Its effects on cell cycle were analyzed by flow cytometry and western blotting. Wound healing, Boyden chamber, western blotting and gelatin zymography assays were utilized to assess migration and invasion abilities of cells overexpressed with ZFP403. The xenograft model in nude mice was used to elucidate the role of ZFP403 on tumorigenesis in vivo.

Results: Compared with normal ovarian tissues and cells, significantly lower expression levels of ZFP403 were observed in ovarian cancer tissues and cells. Ectopic overexpression of ZFP403 in ovarian cancer cells dramatically suppressed cell proliferation by inducing cell cycle arrest at G2/M phase. Moreover, overexpression of ZFP403 in SK-OV3 cells inhibited cell migration and invasion. Xenograft study also demonstrated that overexpression of ZFP403 suppressed the tumor growth in vivo.

Conclusion: The effects of ZFP403 on cell proliferation and metastasis suggest that it may serve as a tumor suppressor in ovarian cancer.

Keywords: Metastasis; Ovarian cancer; Proliferation; ZFP403.