Novel agent #2714 potently inhibits lung cancer growth by suppressing cell proliferation and by inducing apoptosis in vitro and in vivo

作者：Lu, Wenjie; Sun, Qianqian; Chen, Bo; Li, Yan; Xu, Youzhi^*; Wang, Siying^*

来源：Molecular Medicine Reports, 2019, 19(6): 4788-4796.

DOI：10.3892/mmr.2019.10114

• #2714
• small molecular candidate
• Wnt
• beta-catenin pathway
• apoptosis
• anti-proliferation

The use of small molecule compounds to inhibit cell proliferation is one of the most promising approaches in cancer therapy. In the present study, a cell viability assay, flow cytometry analysis, western blotting and mouse xenograft models were used to investigate the anticancer activities of #2714 and its underlying mechanisms in lung cancer. The present in vitro results suggested that #2714 significantly inhibited the viability of the human non-small cell lung cancer line SPC-A1 in a concentration- and time-dependent manner, with a half-maximal inhibitory concentration value of 5.54 mu M after 48 h of treatment. Additionally, #2714 inhibited SPC-A1 cell proliferation via the Wnt/beta-catenin pathway and by impairing mitochondrial membrane potential. The protein expression levels of Wnt 3a, Wnt 5a/b, phosphorylated (p)-beta-catenin, p-glycogen synthase kinase 3 beta, and p-mitogen-activated protein kinase 14 were downregulated following treatment with #2714. Furthermore, using a mouse xenograft model, #2714 was identified to significantly inhibit tumor growth and to decrease cancer cell proliferation in vivo. #2714 may represent a novel effective anticancer compound targeting lung cancer cells. Additionally, #2714 was able to induce apoptosis and decrease cell proliferation in SPC-A1 cells via the Wnt/beta-catenin pathway.

• 单位
  安徽医科大学; 四川大学