Anlotinib Inhibits Proliferation and Induces Apoptosis in B-cell Acute Lymphoblastic Leukemia by Targeting the BTK and AKT/mTOR Pathway

Abstract

Background: Acute lymphoblastic leukemia (ALL) is the second most common acute leukemia in adults, whose known drug treatments are limited and expensive. Objective: This investigation aimed to investigate the therapeutic potential of anlotinib in B-cell acute lymphoblastic leukemia (B-ALL). Methods: The B-ALL cell lines Nalm-6 and BALL-1 were used to verify the therapeutic potential of anlotinib in BALL. The cell activity was measured by Cell Counting Kit-8. Apoptosis was detected by Annexin V-FITC/PI double staining combined with flow cytometry. Afterward, the binding capacity of anlotinib to the critical protein was predicted by molecular docking, and the protein changes in the related pathways downstream of the target proteins were verified by western blot. Finally, the effect of anlotinib on the survival rate was verified in B-ALL nude mice. Results: Anlotinib inhibited the proliferation of the B-ALL cell lines, Nalm-6, and BALL-1, and promoted apoptosis. Molecular docking results showed that it had the potential binding ability to BTK. Western blot revealed that anlotinib was able to inhibit the phosphorylation of BTK, AKT, and mTOR, thereby inhibiting the proliferation of B-ALL cells. In addition, anlotinib suppressed weight loss and prolonged the survival time of mice. Conclusion: To summarize, anlotinib can inhibit the proliferation of B-ALL and promotes apoptosis by inhibiting the phosphorylation of BTK and AKT, and mTOR.