研究动态
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抑制血红素加氧酶 1 可抑制生长、迁移和侵袭,并调节肿瘤浸润 CD8 T 细胞和葡萄膜黑色素瘤。

Inhibition of Heme Oxygenase 1 Suppresses Growth, Migration, and Invasion, and Regulates Tumor-Infiltrating CD8+ T Cells and in Uveal Melanoma.

发表日期:2024 Aug 01
作者: Chen Hou, Qi Wan, Lirong Xiao, Qing Xiao, Meixia Zhang, Naihong Yan
来源: Cellular & Molecular Immunology

摘要:

转移性葡萄膜黑色素瘤(UM)治疗困难,迫切需要有效的治疗方法。我们旨在探讨血红素加氧酶1(HO-1)在UM中的作用,为UM提供新的治疗策略。利用生物信息学分析HMOX1与免疫在UM及其他肿瘤中的关系。使用 Cell Counting Kit-8、Western blot、免疫荧光染色、伤口愈合和 Transwell 检测。采用小鼠皮下移植的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强相关。 ZnPP在体外可抑制UM细胞的生长,促进细胞凋亡,使细胞周期阻滞在G0/G1期。 HO-1敲除可以有效抑制UM细胞的增殖。在皮下肿瘤移植模型中,ZnPP有效抑制UM的生长并促进CD8 T细胞的浸润。这些结果表明,针对UM中的HO-1具有独立靶向免疫治疗或辅助免疫治疗的潜力。
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.