Center for Plastic & Reconstructive Surgery, Department of Plastic and Reconstructive Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, People's Republic of China.
Immunopharmacol Immunotoxicol. 2022 Aug;44(4):541-547. doi: 10.1080/08923973.2022.2062380. Epub 2022 Apr 22.
The overall survival of melanoma patients remains poor despite advancements in surgical treatment and targeted therapies. Therefore, there is a need to develop new therapeutic strategies for melanoma. 2-methoxyestradiol (2-ME) is a major metabolite of estrogen that has been shown to have anti-tumor effects against many malignancies. However, the effects and mechanisms of action of 2-ME against melanoma remain unclear. Melanoma cells (B16) were treated with 2-ME in vitro. Cell proliferation was detected by CCK8 and clone formation, transwell was carried out to measure the migration of B16 cells with or without 2-ME. Flow cytometry was performed to measure the apoptosis and cell cycle. C57BL/6 mice were used for tumor-bearing of B16 cells, tumor volumes were measured once a day, and sacrificed after it was over 2000 mm3, then immunofluorescence was implemented to examine the marker of CD3, CD8 and PD-L1. In our study, we found that 2-ME significantly affected the proliferation, migration, apoptosis, and cell cycle of melanoma in vitro. Our results also showed that 2-ME had strong anti-tumor effects against melanoma in vivo and increased the infiltration of tumor-specific cytotoxic lymphocytes CD8+ T cells in the tumor microenvironment. Besides, PD-L1 expression in tumor cells was significantly higher in the 2-ME-treated group than in the control group, indicating that 2-ME could exhibit stronger anti-tumor effects against melanoma if combined with PD-1 blockade therapy. 2-ME suppresses melanoma in vivo and in vitro and is a promising synergistic enhancer of PD-1 blockade immunotherapy.
尽管在手术治疗和靶向治疗方面取得了进展，但黑色素瘤患者的总体生存率仍然较差。因此，需要开发新的黑色素瘤治疗策略。2-甲氧基雌二醇（2-ME）是雌激素的主要代谢产物，已被证明对许多恶性肿瘤具有抗肿瘤作用。然而，2-ME 对黑色素瘤的作用机制尚不清楚。在体外用 2-ME 处理黑色素瘤细胞（B16）。通过 CCK8 和克隆形成检测细胞增殖，用或不用 2-ME 进行 Transwell 以测量 B16 细胞的迁移。通过流式细胞术检测细胞凋亡和细胞周期。使用 C57BL/6 小鼠进行 B16 细胞荷瘤，每天测量肿瘤体积，超过 2000mm3 后处死，然后进行免疫荧光以检查 CD3、CD8 和 PD-L1 的标志物。在我们的研究中，我们发现 2-ME 显著影响黑色素瘤在体外的增殖、迁移、凋亡和细胞周期。我们的结果还表明，2-ME 对体内黑色素瘤具有很强的抗肿瘤作用，并增加了肿瘤微环境中肿瘤特异性细胞毒性淋巴细胞 CD8+T 细胞的浸润。此外，与对照组相比，2-ME 处理组肿瘤细胞中 PD-L1 的表达明显更高，表明 2-ME 与 PD-1 阻断疗法联合使用可能对黑色素瘤表现出更强的抗肿瘤作用。2-ME 在体内和体外抑制黑色素瘤，是 PD-1 阻断免疫治疗的有前途的协同增强剂。
