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Silencing Wnt2B by siRNA Interference Inhibits Metastasis and Enhances Chemotherapy Sensitivity in Ovarian Cancer
  1. Hongyan Wang, MD*,
  2. Liangsheng Fan, MD*,
  3. Xi Xia, PhD,
  4. Yumei Rao, MD,
  5. Quanfu Ma, MD§,
  6. Jie Yang, MD*,
  7. Yunping Lu, MD*,
  8. Changyu Wang, MD§,
  9. Ding Ma, MD, PhD§ and
  10. Xiaoyuan Huang, MD§
  1. *Cancer Biology Research Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei;
  2. Department of Obstetrics and Gynecology, South Mountain Hospital of Guangdong Medical College, Shenzhen, Guangdong;
  3. Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan; and
  4. §Department of Gynecologic Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
  1. Address correspondence and reprint requests to Xiaoyuan Huang, MD, Ding Ma, MD, PhD, and Changyu Wang, MD, Department of Gynecologic Oncology, Tongji Hospital, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, Hubei 430030, PR China. E-mail: huangxy@tjh.tjmu.edu.cn.

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.

  • Wnt2B
  • Ovarian cancer
  • Metastasis
  • Drug resistance

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Footnotes

  • Wang and Fan contributed equally to this work.

  • This work was supported by a grant from the National Natural Science Foundation of China (30901587, 81101971), “973” program of China (2009CB521808) and National Natural Science Foundation of Guangdong Province (2011040006012).

  • The authors declare that there are no conflicts of interest.

  • Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal’s Web site (www.ijgc.net).

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