血红素加氧酶 1 的抑制作用可抑制葡萄膜黑色素瘤的生长、迁移和侵袭，并调节肿瘤浸润的 CD8+T 细胞。

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

机构信息

Research Laboratory of Macular Disease, West China Hospital, Sichuan University, Chengdu, China.

Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China.

出版信息

Invest Ophthalmol Vis Sci. 2024 Aug 1;65(10):37. doi: 10.1167/iovs.65.10.37.

DOI:10.1167/iovs.65.10.37

PMID:39186260

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11361405/

Abstract

PURPOSE

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

These results indicate that targeting HO-1 in UM has the potential for independent targeted immunotherapy or adjuvant immunotherapy.

摘要

目的

葡萄膜黑色素瘤（UM）的转移治疗较为困难，急需有效的治疗方法。本研究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。

方法

采用生物信息学方法分析 UM 与其他肿瘤中 HMOX1 与免疫的关系。通过细胞计数试剂盒-8（CCK-8）、Western blot、免疫荧光染色、划痕愈合和 Transwell 实验检测，在小鼠中建立皮下移植 UM 肿瘤模型以验证治疗效果。

结果

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呈强相关。ZnPP 可抑制 UM 细胞的生长，促进细胞凋亡，并在体外阻断细胞周期于 G0/G1 期。HO-1 敲除可有效抑制 UM 细胞的增殖。ZnPP 可有效抑制 UM 的生长，并促进 CD8+T 细胞在皮下肿瘤移植模型中的浸润。