Department of Radiation and Medical Oncology, Zhongnan Hospital, Hubei Cancer Clinical Study Center, Wuhan University, Wuhan, China.
Biochem Biophys Res Commun. 2012 Jan 6;417(1):62-6. doi: 10.1016/j.bbrc.2011.11.055. Epub 2011 Nov 25.
Lung cancer is the leading cause of cancer related deaths worldwide. It is necessary to better understand the molecular mechanisms involved in lung cancer in order to develop more effective therapeutics for the treatment of this disease. Recent reports have shown that Wnt signaling pathway is important in a number of cancer types including lung cancer. However, the role of Frizzled-8 (Fzd-8), one of the Frizzled family of receptors for the Wnt ligands, in lung cancer still remains to be elucidated. Here in this study we showed that Fzd-8 was over-expressed in human lung cancer tissue samples and cell lines. To investigate the functional importance of the Fzd-8 over-expression in lung cancer, we used shRNA to knock down Fzd-8 mRNA in lung cancer cells expressing the gene. We observed that Fzd-8 shRNA inhibited cell proliferation along with decreased activity of Wnt pathway in vitro, and also significantly suppressed A549 xenograft model in vivo (p<0.05). Furthermore, we found that knocking down Fzd-8 by shRNA sensitized the lung cancer cells to chemotherapy Taxotere. These data suggest that Fzd-8 is a putative therapeutic target for human lung cancer and over-expression of Fzd-8 may be important for aberrant Wnt activation in lung cancer.
肺癌是全球癌症相关死亡的主要原因。为了开发更有效的治疗这种疾病的方法，有必要更好地了解肺癌中涉及的分子机制。最近的报告表明，Wnt 信号通路在包括肺癌在内的多种癌症类型中都很重要。然而，Wnt 配体的 Frizzled 家族受体之一 Frizzled-8（Fzd-8）在肺癌中的作用仍有待阐明。在本研究中，我们显示 Fzd-8 在人肺癌组织样本和细胞系中过表达。为了研究 Fzd-8 过表达在肺癌中的功能重要性，我们使用 shRNA 敲低表达该基因的肺癌细胞中的 Fzd-8 mRNA。我们观察到 Fzd-8 shRNA 在体外抑制细胞增殖以及 Wnt 通路活性降低，并且在体内 A549 异种移植模型中也显著抑制（p<0.05）。此外，我们发现通过 shRNA 敲低 Fzd-8 可使肺癌细胞对化疗药物 Taxotere 敏感。这些数据表明 Fzd-8 是人类肺癌的潜在治疗靶点，Fzd-8 的过表达可能对肺癌中异常的 Wnt 激活很重要。
