Journal
CANCER MANAGEMENT AND RESEARCH
Volume 12, Issue -, Pages 4937-4948Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/CMAR.S252181
Keywords
anlotinib; colorectal cancer; angiogenesis; proliferation; tyrosine kinase inhibitor
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Funding
- Southwest Medical University
- Research Foundation of the Science and Technology Department of Sichuan Province [0903-00021897]
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Background: Anlotinib is a highly potent multi -target tyrosine kinase inhibitor, with very good anti -tumor activity against a variety of solid tumors. However, its effect on colorectal cancer (CRC) is not yet clearly understood. The objective of this study was to investigate the anti -tumor effect and underlying mechanism of anlotinib in the pathogenesis of CRC. Materials and Methods: Effects of anlotinib on CT26 cells proliferation and microvessel formation in endothelial cells were determined by MTT assay and tube formation assay. Cell migration and invasion were analyzed by using the wound healing assay and transwell assay. Cell cycle and apoptosis were detected by flow cytometry. A CRC xenograft mouse model was used for conducting in -vivo studies to verify the effect of anlotinib. The expression of Ki-67 and CD31 in the tumor tissue was detected by immunohistochemistry and protein expression was measured by Western blot. Results: In -vitro studies revealed that anlotinib inhibited the proliferation, migration, and invasion of CT26 cells and the tube formation of HUVECs in a dose -dependent manner. Anlotinib also signi ficantly induced cell apoptosis and G2/M arrest. It effectively inhibited tumor growth and prolonged survival time in the CRC xenograft mouse model. Immunohistochemical analysis of the tumor tissue revealed that anlotinib downregulated CD31 and Ki-67 which are the biomarkers of microvessel density and proliferation. Furthermore, anlotinib was able to inhibit the activation of VEGFR-2/AKT and FGFR, PDGFR ? and their downstream signaling ERK. Conclusion: The findings of the present study suggested that anlotinib suppressed cell proliferation and angiogenesis via inhibition of AKT/ERK signaling pathway in colorectal cancer and could be a novel therapeutic strategy for treatment of CRC.
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