Department of Respiratory Medicine, Jinling Hospital, Southern Medical University, Nanjing, Jiangsu, China.
Eur Rev Med Pharmacol Sci. 2018 Mar;22(5):1323-1332. doi: 10.26355/eurrev_201803_14474.
Aberrant activation of (Wingless and mouse homolog Int-1) Wnt/β-catenin signaling pathways closely involved in the occurrence and progression of several types of human malignancies. This research was undertaken to elucidate the important role of (Wingless and mouse homolog Int-1) in lung cancer.
Wnt3 expression in lung cancers and their respective normal tissues were examined by immunoblotting and immunohistochemistry. Then, Wnt3 was regulated with RNA interference (RNAi) technology in human lung cancer A549 cells, and the cell proliferation, cell cycle, cell invasion/metastasis, and apoptosis were evaluated.
In all cases, Wnt3 expression was significantly elevated in lung cancers compared with normal tissues. Knocking down Wnt3 in A549 lung cancer cells by small interfering RNAs transfection led to a distinct reduction of Wnt3 in both transcript and protein levels. Knockdown of Wnt3 expression in lung cancer cells inhibited the expression of β-catenin and cyclin D1 genes in Wnt/β-catenin pathway. It also significantly blocked cellular proliferation, delayed cell cycle and suppressed cell invasion/metastasis, accompanied by a higher apoptosis rate.
We conclude that the upregulation of Wnt3 plays a crucial role in lung tumorigenesis by inducing proliferation, migration, and invasion and inhibiting apoptosis of cancer cells. Wnt3 might be a potential target for the treatment of lung cancer.
（无翅型和鼠类同源物 Int-1）Wnt/β-连环蛋白信号通路的异常激活与多种人类恶性肿瘤的发生和进展密切相关。本研究旨在阐明（无翅型和鼠类同源物 Int-1）在肺癌中的重要作用。
采用免疫印迹法和免疫组织化学法检测肺癌及其相应正常组织中的 Wnt3 表达。然后，采用 RNA 干扰（RNAi）技术调控人肺癌 A549 细胞中的 Wnt3，评估细胞增殖、细胞周期、细胞侵袭/转移和细胞凋亡。
在所有病例中，肺癌组织中的 Wnt3 表达明显高于正常组织。通过小干扰 RNA 转染敲低 A549 肺癌细胞中的 Wnt3，导致转录本和蛋白水平的 Wnt3 明显减少。肺癌细胞中 Wnt3 表达的敲低抑制了 Wnt/β-连环蛋白通路中β-连环蛋白和细胞周期蛋白 D1 基因的表达。它还显著阻断了细胞增殖，延迟了细胞周期，抑制了细胞侵袭/转移，并伴随着更高的细胞凋亡率。
我们得出结论，Wnt3 的上调通过诱导癌细胞的增殖、迁移和侵袭以及抑制细胞凋亡，在肺癌发生中起着关键作用。Wnt3 可能是治疗肺癌的潜在靶点。
