Study on the CHJ01 antitumor activity and mechanism via targeting sphingosine kinase 1 in A549 cells
Caiyu Liu, Shengmei Gao, Bo Liu, Feipeng Zhang, Yanling Mu, Fuwen Wang, Yan Li
Abstract
The SphK1 inhibitor development is of great importance for the treatment of non-small cell lung cancer (NSCLC). In this study, CHJ01 which has been previously shown anti-tumor effects was introduced to investigate the detailed antitumor mechanism both in vitro and in vivo . CHJ01 inhibited the A549 cell proliferation, migration, and invasion significantly and showed cytotoxicity to A549. CHJ01 induced G0/G1 cell cycle arrest by increasing ceramide levels and altered the expression of TRAF2, Bcl-2, Bax and RELA. CHJ01 inhibited the TRAF2/ NF-κB signaling pathway and promoted apoptosis by downregulating Bcl-2 and upregulating Bax. In vivo anti-tumor effects were investigated using a nude mouse ectopic tumor model. CHJ01 reduced the volumes and weights of xenograft tumor in nude mice. CHJ01 induced apoptosis by HE staining and immunohistochemistry assay. These results indicated that CHJ01 can be a potential candidate for the treatment of NSCLC.