Cancer Biology Research Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
Int J Gynecol Cancer. 2012 Jun;22(5):755-61. doi: 10.1097/IGC.0b013e3182540284.
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.
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.
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 的过表达被认为通过激活经典的 Wingless 和 INT-1 信号通路参与肿瘤进展。然而，Wnt2B 信号在肿瘤发生中的机制尚不清楚。在这项研究中，我们研究了沉默 Wnt2B 表达是否可以抑制卵巢癌细胞的侵袭性并降低耐药性。
方法/材料：使用了 4 种卵巢癌细胞系，SKOV3、OV2008、A2780 和 C13K。通过 Western blot 研究蛋白水平。通过集落形成测定和 Matrigel 侵袭测定分别确定集落形成能力和侵袭能力。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐测定法测定细胞活力，而通过流式细胞术分析评估细胞凋亡。
在 4 种卵巢癌细胞系中，A2780 细胞和 C13K 细胞表达 Wnt2B，这 2 种细胞系用于分析 Wnt2B 的作用机制。Wnt2B 的下调抑制了细胞集落形成和侵袭性。在用 Wnt2B siRNA 处理的 A2780 细胞或 C13K 细胞中观察到增强的紫杉醇或顺铂敏感性。在用 Wnt2B siRNA 处理的情况下，caspase-9/B 细胞淋巴瘤 2（BCL2）/B 细胞淋巴瘤-xL（BCL-xL）通路和上皮-间充质转化/磷酸化蛋白激酶 B 通路被抑制。
这些数据表明 Wnt2B 确实在卵巢癌转移和耐药性中发挥重要作用。本研究可能为卵巢癌治疗提供新的治疗靶点，并更好地理解卵巢癌治疗。
