Journal of Inflammation Research (Feb 2024)
N-Ethyl-N-Nitrosourea Induced Leukaemia in a Mouse Model: Protective Effect of Icaritin via Inhibition of IL-6/JAK2/STAT3 Pathway Causes Apoptosis
Abstract
Xinjun Hou,1 Yanhui Han,2 Abdurahman Hajinur Hirad,3 Abdullah A Alarfaj,3 Linxiang Liu4 1Department of Traditional Chinese Medicine Hematology, Xin’an People’s Hospital, Luoyang, Henan, 471000, People’s Republic of China; 2Department of Internal Medicine of Traditional Chinese Medicine, Xin’an the Second People’s Hospital, Luoyang, Henan, 471000, People’s Republic of China; 3Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia; 4Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of ChinaCorrespondence: Linxiang Liu, Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China, Email [email protected]: The present study aimed to investigate the protective effect of icaritin (ICT) on ENU-induced leukemia in male mice.Methods: The mice received intraperitoneal injections of 80 mg/kg ENU twice a week for three months for induction of leukemia. Blood smears from these mice showed blast cells, confirming the presence of leukemia. After confirming leukemia, mice were divided into control, ENU-induced leukemia, and leukemia groups (10 mg/kg bw and 20 mg/kg bw) were treated with ICT for 35 days. Blood, spleen, and liver samples were collected for analysis. The expression of IL-6, JAK2, STAT3, as well as inflammatory, pro-apoptotic (Bax), and anti-apoptotic (Bcl-2) proteins were evaluated using qPCR, immunohistochemistry, and immunofluorescence techniques.Results: The study found that ICT inhibited inflammation and the IL-6/JAK2/STAT3 pathway in ENU-induced mice. ICT treatment induced apoptosis in the spleen and liver by activating Bax and downregulating Bcl-2. The findings provide novel evidence that ICT acts as a dual inhibitor of IL-6/JAK2/STAT3 signaling, promoting apoptosis and playing an essential role in anti-leukemic activity.Conclusion: These results suggest that ICT has potential as a therapeutic target for treating leukemia, offering a novel approach to leukemia treatment through inhibiting the IL-6/JAK2/STAT3 pathway and induction of apoptosis.Keywords: N-ethyl-n-nitrosourea, leukaemia, ICT, IL-6/JAK2/STAT3, inflammation, apoptosis
