Wnt3 knockdown sensitizes human non-small cell type lung cancer (NSCLC) cells to cisplatin via regulating the cell proliferation and apoptosis.

Abstract

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.