Abstract 4051: Anlotinib inhibits the progress of colorectal cancer cells by antagonizing glycolysis & JAK2-STAT3 signaling

Background: Anlotinib is a novel multi-target tyrosine kinase receptor inhibitor (TKI) that has been proved to treat advanced NSCLC as a third-line regime in China. This study designed to investigate the effectiveness & possible mechanism of anlotinib colorectal cancer (CRC) therapy. Methods: CCK-8 assay & CyQUANT NF assay were used to detect the sensitivity of CRC cells to DDP & anlotinib. Real time quantitative polymerase chain reaction was used to detect the mRNA level of hub genes. The protein expression of pVEGFR2, cleaved PARP, cleaved caspase 3, JAK2, pJAK2, STAT3 & PSTAT3 were determined by western blot. The roles of DDP & anlotinib in the progression, invasion & metastasis of CRC cells were evaluated by colony formation, wound healing & trans-well assay. Lactate release & glucose consumption were measured to investigate glucose metabolism. Cell apoptosis was analyzed by Hoechst33342 fluorescence staining & flow cytometer. Results: We found that anlotinib may improve the treatment of CRC by blocking the effects of VEGFA. Subsequently, in vitro assays demonstrated that anlotinib &/or DDP inhibited cell proliferation, migration & invasion & also activated apoptosis in human colorectal cancer cells. Additionally, glucose metabolism in CRC HCT-116 & LOVO cells was suppressed by anlotinib &/or DDP. In other hand, anlotinib &/or DDP may improve the treatment of CRC by inhibiting JAK2-STAT3 signaling pathway. Conclusions: Our preclinical studies showed that anlotinib inhibited cell proliferation, invasion, migration & activated apoptosis by antagonizing glycolysis & JAK2-STAT3 signaling. Combination chemotherapy of anlotinib with cisplatin is more sensitive to CRC. Citation Format: Zhenxian Jia, Zhi Zhang, Ze Li, Ang Li, Yuning Xie, Hongjiao Wu, Zhenbang Yang, Hongmei Zhang, Xuemei Zhang. Anlotinib inhibits the progress of colorectal cancer cells by antagonizing glycolysis & JAK2-STAT3 signaling [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4051.