血红素氧酶1的抑制作用抑制生长，迁移和侵袭，并调节肿瘤浸润的CD8+ T细胞和紫菜叶黑色素瘤
Inhibition of Heme Oxygenase 1 Suppresses Growth, Migration, and Invasion, and Regulates Tumor-Infiltrating CD8+ T Cells and in Uveal Melanoma
影响因子:4.70000
分区:医学2区 / 眼科学2区
发表日期:2024 Aug 01
作者:
Chen Hou, Qi Wan, Lirong Xiao, Qing Xiao, Meixia Zhang, Naihong Yan
摘要
转移性卵巢黑色素瘤（UM）治疗很困难，迫切需要有效的治疗。我们的目的是探索血红素加氧酶1（HO-1）在UM中的作用，并为U.Mioformatics提供新的治疗策略来分析HMOX1与UM肿瘤中的HMOX1与免疫之间的关系。使用了细胞计数KIT-8，蛋白质印迹，免疫荧光染色，伤口愈合和Transwell分析。在小鼠中使用皮下移植的UM肿瘤模型来验证治疗效果。在UM中，HMOX1的表达水平与免疫评分和各种免疫细胞的浸润水平密切相关。 ZNPP可以抑制UM细胞的生长，促进细胞凋亡，并在G0/G1相时阻止细胞周期。 HO-1敲除可以有效抑制UM细胞的增殖。 ZNPP有效抑制了UM的生长，并促进了皮下肿瘤移植模型中CD8+ T细胞的浸润。这些结果表明，UM中的HO-1靶向具有独立的靶向免疫疗法或辅助免疫疗法的潜力。
Abstract
Metastatic uveal melanoma (UM) treatment is difficult, and effective treatments are urgently needed. We aimed to explore the role of heme oxygenase 1 (HO-1) in UM and provide new therapeutic strategies for UM.Bioinformatics was used to analyze the relationship between HMOX1 and immunity in UM and other tumors. Cell Counting Kit-8, Western blot, immunofluorescence staining, wound healing, and Transwell assays were used. A subcutaneous transplanted UM tumor model was used in mice to verify the therapeutic effect.In UM, the expression level of HMOX1 was strongly correlated with the immune score and the infiltration level of various immune cells. ZnPP can inhibit the growth of UM cells, promote cell apoptosis, and block the cell cycle at G0/G1 phase in vitro. HO-1 knockout can effectively inhibit the proliferation of UM cells. ZnPP effectively inhibited the growth of UM and promoted the infiltration of CD8+ T cells in a subcutaneous tumor transplantation model.These results indicate that targeting HO-1 in UM has the potential for independent targeted immunotherapy or adjuvant immunotherapy.