Abstract
Axl, a member of the TAM (Tyro3, AXL, Mer) receptor tyrosine kinase family, plays critical roles in cell growth, proliferation, apoptosis, and migration. In the present study, we demonstrated that the anti-cancer activity of bufalin, a major bioactive component of the Chinese traditional medicine Chan Su, is mediated by the down-regulation of Axl in non-small-cell lung cancer (NSCLC) cells. We observed the inhibitory effect of bufalin on the proliferation of A549 and H460 NSCLC cells and the clonogenicity of these cells was reduced by bufalin treatment in a dose-dependent manner. Next, we found that the protein level of Axl was decreased in proportion to the concentration of bufalin in both A549 and H460 cells. Moreover, the promoter activity of the Axl gene was decreased by bufalin in a dose- and time-dependent manner, indicating that bufalin down-regulates Axl gene expression at the transcriptional level. We further examined if the anti-proliferative property of bufalin is influenced by Axl at the protein level. Axl overexpression attenuated the effect of bufalin in inhibiting cell proliferation and colony formation and inducing apoptosis in H460 cells, while knockdown of Axl gene expression induced the opposite effect. Taken together, our data indicate that the anti-proliferative and pro-apoptotic effects of bufalin were associated with the protein level of Axl, suggesting that Axl is a potent therapeutic target of bufalin in suppressing proliferation and inducing apoptosis in NSCLC cells.
Highlights
Lung cancer is the most frequently diagnosed cancer in both men and women (14.5% and 8.4% of all diagnosed cases, respectively) and represents the leading cause of death in terms of mortality rate [1]
We demonstrated that bufalin inhibits cell proliferation and induces apoptosis in non-small-cell lung cancer (NSCLC) cells, and these phenomena were found to be associated with the down-regulation of Axl expression
We first examined the anti-proliferative effect of bufalin in the NSCLC cell lines A549 and H460
Summary
Lung cancer is the most frequently diagnosed cancer in both men and women (14.5% and 8.4% of all diagnosed cases, respectively) and represents the leading cause of death in terms of mortality rate [1]. It is divided into two types that include small-cell lung carcinoma (15% of all cases) and non-small-cell lung carcinoma (NSCLC, 85%) [2] Classic approaches such as surgery, adjuvant therapy, chemotherapy, and radiotherapy have been commonly used for treatment; customized therapy targeting appropriate oncogenes and immunotherapy have both been recently introduced. Axl is reportedly correlated with highly aggressive cancers [13,14,15], epithelial-to-mesenchymal transition [16,17], and chemoresistance [17,18,19] This protein is a practical therapeutic target for successful cancer treatment, and small molecules that inhibit Axl have been exploited. BGB324 (R248) is a selective Axl inhibitor and the first candidate to be tested in phase I clinical trials for treatment of acute myeloid leukemia or NSCLC [20,21]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
