Anlotinib Suppresses Colorectal Cancer Proliferation and Angiogenesis via Inhibition of AKT/ERK Signaling Cascade

• Main Authors: Yang Q, Ni L, Imani S, Xiang Z, Hai R, Ding R, Fu S, Wu J, Wen Q
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-06-01
• Series: Cancer Management and Research
• Subjects: anlotinib; colorectal cancer; angiogenesis; proliferation; tyrosine kinase inhibitor
• Online Access: https://www.dovepress.com/anlotinib-suppresses-colorectal-cancer-proliferation-and-angiogenesis--peer-reviewed-article-CMAR

Qian Yang,1,* Laichao Ni,1,* Saber Imani,1,* Zhangqiang Xiang,1 Rui Hai,1 Ruilin Ding,1 Shaozhi Fu,1 Jing bo Wu,1,2 Qinglian Wen1 1Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, People’s Republic of China; 2Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qinglian WenDepartment of Oncology, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, 3-319 Zhongshan Road, Luzhou, Sichuan 646000, People’s Republic of ChinaTel/ Fax [phone]Email [e-mail]: 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 significantly 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, PDGFRβ 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.Keywords: anlotinib, colorectal cancer, angiogenesis, proliferation, tyrosine kinase inhibitor