Aim of the study
To investigate the influence of BBM on the progression of colorectal cancer (CRC) and further explore the underlying mechanism of BBM based on the RTKs/Akt signaling pathway. Materials and
Conclusion
Taken together, all the results as presented above suggest that BBM as a novel multitargeted receptor tyrosine kinase inhibitor plays a crucial role in the inhibitory effect of CRC and may be a promising therapeutic agent for the CRC in clinic.
Methods
In vitro, cell viability and colony formation were conducted to detect BBM inhibitory of CRC cell lines. Transwell was detected the ability of migration and invasion by BBM. Apoptosis detection assay, cell cycle assay and the measurement of ROS were detected to confirm the inductive effect of cell apoptosis. RT-qPCR and Western blot to clarify the specific mechanism of anticancer. Finally, we conducted HE staining, Ki67, Tunnel and immunochemistry were confirmed the anti-colorectal cancer activity of BBM from vivo study.
Results
We found that BBM could inhibit CRC cell lines growth. Moreover, BBM presented an inhibitory effect the ability of migration and invasion in CRC cells. Furthermore, the occurrence of apoptosis was involved in the anti-colorectal cancer role of BBM. BBM also triggered ROS accumulation in CRC cells that might be a key factor for the inductive effect of BBM in cell apoptosis. Cell cycle assay revealed that BBM induced the arrest of G1-S phase and increased the p21 levels but decreased CyclinE1, CyclinE2, CDK6, CyclinD1. RT-qPCR manifested that the down-regulation effect of BBM on AKT1, EGFR, PDGFRα and FGFR4 genes. The results also showed that BBM could decreased the expression levels of phosphor-AKT, PDGFRα, PDGFRβ, EGFR, FGFR3 and FGFR4 which belong to RTKs family. Consistently, BBM remarkably suppressed tumor xenograft growth in nude mice.