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Cyy260, a Novel Small Molecule JAK2 Inhibitor, Suppresses Cell Growth in Non-Small Cell Lung Cancer

Background: Non-small cell lung cancer (NSCLC) is a malignant tumor that accounts for the most new cancer cases and cancer-related deaths worldwide. It is particularly important to study therapies that target cancer cells and to find low-toxicity, high-efficiency anticancer drugs. Cyy260 is a novel small molecule JAK2 inhibitor with good antitumor effect. 
 
Methods: MTT and clone formation experiments were used to evaluate the effect of Cyy260 on cell proliferation. Transwell and scratch experiments were used to evaluate the effect of Cyy260 on cell migration. Flow cytometry was used to detect cell apoptosis and cell cycle changes. Downregulation and overexpression of the JAK2 protein were assessed to study the mechanism of Cyy260 inhibition of JAK2/STAT3 signaling. A xenograft tumor model was used to explore the effect of Cyy260 on tumor growth in vivo. 
 
Findings: Cyy260 had a concentration- and time-dependent inhibitory effect on NSCLC cells, regulated apoptosis and inhibited cell proliferation. Further analysis of molecular mechanisms showed that the JAK2/STAT3 signaling pathway was involved in the antitumor effect mediated by Cyy260 in vitro and in vivo. 
 
Interpretation: Cyy260 is a novel inhibitor of the JAK2/STAT3 pathway thus may have potential in therapy of NSCLC and other cancers. 
 
Funding: This work was financially supported by the National Natural Science Foundation of China (81973168), Natural Science Foundation of Zhejiang Province (LY21H300005 and LQ21H310007) and Wenzhou Municipal Science and Technology Bureau (ZY2020025 and Y20190056). 
 
Declaration of Interest: The authors declare that they have no competing interests. 
 
Ethical Approval: All animal studies were performed with an approved protocol by the Institutional Animal Care and Use Committee of Wenzhou Medical University.