Therapeutic Potential of Apatinib Against Colorectal Cancer by Inhibiting VEGFR2-Mediated Angiogenesis and β-Catenin Signaling
Received 25 June 2020
Accepted for publication 5 October 2020
Published 29 October 2020 Volume 2020:13 Pages 11031—11044
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 4
Editor who approved publication: Dr Leo Jen-Liang Su
Xiaomin Cai,1,* Bin Wei,1,2,* Lele Li,1,* Xiaofeng Chen,1 Jing Yang,1 Xiaofei Li,1 Xiaozheng Jiang,1 Mu Lv,1 Mingyang Li,1 Yumeng Lin,3 Qiang Xu,3 Wenjie Guo,3 Yanhong Gu1
1Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Oncology, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huai’an 223300, People’s Republic of China; 3State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yanhong Gu
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, People’s Republic of China
Email [email protected]
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing 210023, People’s Republic of China
Email [email protected]
Purpose: Apatinib is an inhibitor of VEGFR2 (vascular endothelial growth factor receptor 2) that has attracted a great deal of attention due to its promotion of anticancer activity. In the present study, we investigated the therapeutic effects of apatinib against colorectal cancer (CRC) and examined the underlying mechanism.
Materials and Methods: Both in vivo and in vitro assays were conducted to study the effect of apatinib on CRC. To elucidate the associated mechanism, RNA-seq (transcriptome) analysis was conducted on apatinib-treated HCT116 cells.
Results: Apatinib showed antiproliferative and proapoptotic effects, induced G0/G1 arrest and blocked cell migration and invasion in CRC. An analysis of the mechanism associated with apatinib activity demonstrated that by interacting with VEGFR2, apatinib decreased p-Src, p-Akt, and p-GSK3β levels, which further increased β-catenin ubiquitination and reduced the nuclear translocation of β-catenin. Furthermore, apatinib strongly suppressed CT26 cell growth in mouse xenograft models by inhibiting β-catenin signaling and angiogenesis.
Conclusion: Overall, the results of the present study here indicated that by inhibiting the VEGFR2-β-catenin-mediated malignant phenotype, apatinib significantly suppresses the growth of CRC, suggesting that the use of apatinib is a promising therapeutic strategy for CRC.
Keywords: apatinib, colorectal cancer, VEGFR2, angiogenesis, β-catenin
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