A monoclonal antibody against Wnt-1 induces apoptosis in human cancer cells
A monoclonal antibody against Wnt-1 induces apoptosis in human cancer cells
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DOI：
10.1016/s1476-5586(04)80048-4
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发表时间：
2004-01-01
期刊：
影响因子：
4.8
通讯作者：
Jablons, DM
中科院分区：
文献类型：
--
作者：
He, B;You, L;Jablons, DM
无翅型（Wnt）/β-连环蛋白信号通路的异常激活与多种人类癌症相关。关于Wnt配体在人类致癌作用中的作用知之甚少。为了测试Wnt-1信号是否是人类癌细胞中的生存因子，从而可以作为潜在的癌症治疗靶点，我们研究了抑制Wnt-1信号在多种人类癌细胞系中的作用，包括非小细胞肺癌、乳腺癌、间皮瘤和肉瘤。用单克隆抗体和RNA干扰（RNAi）抑制Wnt-1信号通路。我们发现，单克隆抗Wnt-1抗体的孵育诱导细胞凋亡，并导致过表达Wnt-1的癌细胞下游蛋白质的变化。相反，在抗体孵育后缺乏或具有最小Wnt-1表达的细胞中未检测到凋亡。在过表达Wnt-1的癌细胞中靶向Wnt-1的RNAi表现出类似的下游蛋白质变化和凋亡诱导。该抗体还在体内抑制肿瘤生长。我们的研究结果表明，单克隆抗Wnt-1抗体和Wnt-1 siRNA抑制Wnt-1信号转导，并能诱导人癌细胞凋亡。这些发现有望成为癌症的新治疗策略。
Aberrant activation of the Wingless-type (Wnt)/beta-catenin signaling pathway is associated with a variety of human cancers. Little is known regarding the role that Wnt ligands play in human carcinogenesis. To test whether a Wnt-1 signal is a survival factor in human cancer cells and thus may serve as a potential cancer therapeutic target, we investigated the effect of inhibition of Wnt-1 signaling in a variety of human cancer cell lines, including non small cell lung cancer, breast cancer, mesothelioma, and sarcoma. Both monoclonal antibody and RNA interference (RNAi) were used to inhibit Wnt-1 signaling. We found that incubation of a monoclonal anti-Wnt-1 antibody induced apoptosis and caused downstream protein changes in cancer cells overexpressing Wnt-1. In contrast, apoptosis was not detected in cells lacking or having minimal Wnt-1 expression after the antibody incubation. RNAi targeting of Wnt-1 in cancer cells overexpressing Wnt-1 demonstrated similar downstream protein changes and induction of apoptosis. The antibody also suppressed tumor growth in vivo. Our results indicate that both monoclonal anti-Wnt-1 antibody and Wnt-1 siRNA inhibit Wnt-1 signaling and can induce apoptosis in human cancer cells. These findings hold promise as a novel therapeutic strategy for cancer.