Anlotinib inhibits the progress of colorectal cancer cells by antagonizing VEGFR/JAK2/STAT3 axis

Z.-X. Jia, Z. Zhang, Z. Li, A. Li, Y.-N. Xie, H.-J. Wu, Z.-B. Yang, H.-M. Zhang, X.-M. Zhang

School of Public Health, North China University of Science and Technology, Tangshan, China. jyxuemei@gmail.com

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• Pharmacology

OBJECTIVE: Anlotinib, a novel tyrosine kinase receptor inhibitor (TKI), targets multi-targets, including vascular endothelial growth factor receptor (VEGFR). Increasing evidence suggests that anlotinib exhibits effective anti-tumor activity in various cancer types, such as liver cancer. However, the biological function of anlotinib in the treatment of colorectal cancer (CRC) remains largely unknown. This investigation aims to investigate the function and possible molecular mechanism of anlotinib in CRC therapy.

MATERIALS AND METHODS: Human colorectal cancer cells (HCT-116 and LOVO) were cultured and treated with anlotinib alone or combined with cisplatin (DDP). Thereafter, CCK8 assay, CyQUANT NF assay, and colony formation were used to determine the cytotoxicity property and cell proliferation of colorectal cancer. To evaluate the invasion and metastasis of colorectal cancer cells, we conducted wound healing and trans-well assay. Hoechst33342 fluorescence staining and Flow Cytometry analysis were applied for apoptosis detection. Real-time qPCR and Western blot were used to measure the mRNA or protein level.

RESULTS: Our results showed anlotinib alone or combined with cisplatin inhibited cell proliferation, migration, and invasion and activated apoptosis in colorectal cancer cells. Furthermore, we found that anlotinib inhibiting the phosphorylation level of VEGFR, Janus Kinase 2 (JAK2), and Signal Transducer and Activator of Transcription 3 (STAT3). Combination chemotherapy of anlotinib with cisplatin is more sensitive to colorectal cancer.

CONCLUSIONS: These findings suggested that anlotinib might benefit colorectal cancer therapy by antagonizing VEGFR/JAK2/STAT3 signaling. Our study may provide new insights into novel molecular therapeutic strategies for colorectal cancer.

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