Silencing Wnt2B by siRNA interference inhibits metastasis and enhances chemotherapy sensitivity in ovarian cancer.
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
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.


CONCLUSIONS
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.
Cancer Biology Research Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
Hongyan
H
Wang
Liangsheng
L
Fan
Xi
X
Xia
Yumei
Y
Rao
Quanfu
Q
Ma
Jie
J
Yang
Yunping
Y
Lu
Changyu
C
Wang
Ding
D
Ma
Xiaoyuan
X
Huang
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053453:Caspase 9 / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary*; D017239:Paclitaxel / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D051153:Wnt Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D006023:Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D011838:Radiation-Sensitizing Agents; C115496:WNT2B protein, human; D051153:Wnt Proteins; D051020:bcl-X Protein; D053453:Caspase 9; D017239:Paclitaxel; D002945:Cisplatin