Wnt inhibitor XAV939 suppresses the viability of small cell lung cancer NCI-H446 cells and induces apoptosis

摘要

Small cell lung cancer (SCLC) is the most aggressive type of lung cancer due to a fast tumor doubling time and early hematogenous spread. Advances in the treatment of non-small cell lung cancer using targeted therapies having been made, but no targeted drugs for SCLC have been approved. The Wnt signaling pathway is associated with tumor progression and metastasis; therefore, the inhibition of Wnt/beta-catenin signaling is a strategy for anticancer drugs. Tankyrase 1 (TNKS1) is overexpressed in a number of types of cancer and XAV939 is a small molecule inhibitor of TNKS1 which may inhibit tumor growth. The present study aimed to investigate the potential molecular mechanisms underlying XAV939-induced suppression of the viability of SCLC cells. MTT assays were used to determine the viability-inhibition rate of cells and to identify the drug concentration which optimally inhibited cell viability. Flow cytometry was used to determine whether XAV939 induced apoptosis of SCLC cells, and to analyze the effect of the drug on the cell cycle. The results of the present study identified that XAV939 inhibited the viability of NCI-H446 cells in a dose-dependent manner, but cisplatin inhibited NCI-H446 cell viability in a time-and dose-dependent manner. The combination of XAV939 and cisplatin exhibited a slightly more pronounced inhibition of cell viability at an increased dose of XAV939. In addition, XAV939 markedly induced cell apoptosis of the SCLC cell line H446 by increasing the proportion of cells in the G(0)/G(1) phase, leading to inhibition of the cell cycle. The results of the present study indicated that XAV939 inhibited the viability of the NCI-H446 SCLC cell line by inducing cell apoptosis through the Wnt signaling pathway. Therefore, XAV939 may be useful for the treatment of SCLC.