Silencing Wnt2B by siRNA Interference Inhibits Metastasis and Enhances Chemotherapy Sensitivity in Ovarian Cancer. Issue 5 (1st June 2012)

• Record Type: Journal Article
• Authors: Wang, Hongyan; Fan, Liangsheng; Xia, Xi; Rao, Yumei; Ma, Quanfu; Yang, Jie; Lu, Yunping; Wang, Changyu; Ma, Ding; Huang, Xiaoyuan
• Is Part Of: International journal of gynecological cancer. Volume 22:Issue 5(2012)
• Page Start: 755
• Page End: 761
• Publication Date: 2012-06-01
• Subjects: Wnt2B -- Ovarian cancer -- Metastasis -- Drug resistance; Generative organs, Female -- Cancer -- Periodicals; 616.99465
• DOI: 10.1097/IGC.0b013e3182540284
• Languages: English
• ISSNs: 1048-891X

Abstract

Abstract : Objective: Wnt2B overexpression is thought to be involved in tumor progression through the activation of the canonical Wingless and INT-1 signaling pathway. However, the mechanism of Wnt2B signaling in oncogenesis is unknown. In this study, we investigated whether silencing Wnt2B expression could inhibit the invasiveness of ovarian cancer cells and reduce drug resistance. Methods/Materials: Four ovarian carcinoma cell lines, SKOV3, OV2008, A2780, and C13K, were used. Protein levels were studied by Western blotting. The colony formation ability and invasive ability were determined through colony formation assay and the Matrigel transwell assay, respectively. Cell viability was determined by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay, whereas apoptosis was assessed using flow cytometry analysis. Results: Among the 4 ovarian carcinoma cell lines, the A2780 cells and C13K cells expressed Wnt2B, and these 2 cell lines were used for analyzing the mechanism of Wnt2B. The down-regulation of Wnt2B inhibited cell colony formation and invasiveness. Enhanced paclitaxel or cisplatin sensitivity was observed in A2780 cells or C13K cells treated with Wnt2B siRNA, respectively. In the presence of Wnt2B siRNA treatment, the caspase-9/B-cell lymphoma 2 (BCL2)/B-cell lymphoma-xL (BCL-xL) pathway and the epithelial-mesenchymal transition/phosphorylated protein kinase B pathway were inhibited. Conclusion: These data suggest that Wnt2B indeed plays an important role in ovarian cancer metastasis and drug resistance. This study may provide a new therapeutic target for and a better understanding of ovarian cancer therapy.