A novel Nilotinib derivative N-12 inhibits the proliferation and migration of colon cancer cells through the EMT signaling pathway

Colon cancer ranks among the prevalent malignancies globally, and its proclivity for metastasis significantly contributes to the adverse prognostic outcomes observed in patients. The epithelial-mesenchymal transition (EMT) represents a critical biological process through which tumor cells gain migratory and invasive capabilities. Nilotinib is a selective inhibitor of tyrosine kinases, commonly utilized in the treatment of chronic myeloid leukemia (CML). Prior investigations have demonstrated that the Nilotinib derivative, N-12, exhibits significant antitumor properties. The objective of this study is to elucidate the inhibitory effects of N-12 on the progression of EMT in colon cancer cells. So, the human colon cancer cell line HCT116 was selected for experimentation. Initially, assessments of cell proliferation, migration and invasion were conducted utilizing MTT, colony formation, Edu and Transwell assays. Subsequently, the chick embryo chorioallantoic membrane model was employed to evaluate tumor size and its impact on angiogenesis in vivo. Thereafter, HCT116 cells treated with N-12 underwent RNA sequencing for analysis. Finally, the expression levels of EMT markers in colon cancer cells were determined by Western blot analysis. The results showed that N-12 significantly curtails the proliferation, migration, and invasion of colon cancer cells, and concurrently impedes tumor growth in vivo by influencing angiogenesis within the chick embryo chorioallantoic membrane. Furthermore, RNA sequencing and Western blot analyses have elucidated that the antitumor efficacy of N-12 is attributable to the inhibition of the EMT signaling pathway. These results underscore the therapeutic potential of N-12 in the management of colon cancer and delineate its mechanism of action. In order to investigate the role and mechanism of N_12 in colon cancer, we treated HCT116 cells with N_12 and without treatment. Then, we performed gene expression profiling analysis using RNA seq data from N_12 and DMSO cells.