Abstract:Objective: To investigate the effects of Chrysoeriol (Chry) on the growth and metastasis of human gastric cancer in nude mice and the IL-6/JAK2/STAT3 signaling pathway. Methods: Orthotopic transplantation model of human gastric cancer nude mice was established, and successfully modeled nude mice were randomly separated into a model group, low, medium, and high dose Chry groups (Chry-L, Chry-M, Chry-H groups), and high-dose Chry+JAK2 activator Coumermycin A1 group (Chry-H+CA1 group), 12 animals per group. After subcutaneous injection, the nude mice were killed to take transplanted tumors and weigh them, and the tumor inhibition rate was calculated. HE staining was applied to observe the pathological changes of transplanted tumor tissue. TUNEL staining was applied to detect apoptosis in transplanted tumor tissues. Immunohistochemistry was applied to detect the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) proteins related to migration and invasion of transplanted tumors. Immunoblotting was applied to detect apoptosis of transplanted tumor cells and the expression of IL-6/JAK2/STAT3 signaling pathway related proteins.Results: Compared with the model group, the tumor cell density in the Chry-L, Chry-M, and Chry-H groups decreased, with loose and disordered arrangement, a large number of tumor cells ruptured and necrotic, obvious proliferation of connective tissue, with an increase in nuclear pyknosis and deep staining, a decrease in nuclear division, an increase in apoptotic and necrotic cells, and a reduction in the quality of transplanted tumors, the tumor inhibition rate, cell apoptosis index, and Bax expression increased, the tumor metastasis rate and the expression of Bcl-2, MMP-2, MMP-9, IL-6, p-JAK2/JAK2, p-STAT3/STAT3 reduced, the Chry-H group showed the most obvious changes (P<0.05). Compared with the Chry-H group, the Chry-H+CA1 group showed an increase in tumor cells, relatively neat arrangement, reduced nuclear pyknosis and deep staining, increased nuclear division, obvious tumor necrosis, and increased weight of transplanted tumors, the tumor inhibition rate, cell apoptosis index, and Bax expression decreased, the tumor metastasis rate and the expression of Bcl-2, MMP-2, MMP-9, IL-6, p-JAK2/JAK2, and p-STAT3/STAT3 increased (P<0.05). Conclusion: Chrysoeriol can inhibit the growth and metastasis of human gastric cancer transplanted in nude mice, and its mechanism of action is related to the inhibition of the IL-6/JAK2/STAT3 signaling pathway.
刘霞, 杨东, 张朵朵, 刘晓蕾, 马立东. 金圣草黄素抑制IL-6/JAK2/STAT3通路抑制人胃癌裸鼠原位移植瘤生长和转移[J]. 河北医学, 2024, 30(11): 1766-1771.
LIU Xia, et al. Chrysoeriol Inhibits the Growth and Metastasis of Orthotopic Grafted Human Gastric Cancer in Nude Mice by Inhibiting IL-6/JAK2/STAT3 Pathway. HeBei Med, 2024, 30(11): 1766-1771.
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