福美司坦经皮乳膏通过调控 PI3K-Akt 通路和肿瘤免疫微环境抑制乳腺癌。
The transdermal cream of Formestane anti-breast cancer by controlling PI3K-Akt pathway and the tumor immune microenvironment.
机构信息
Academician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, China.
West China Hospital, Sichuan University, Chengdu, China.
出版信息
Front Immunol. 2023 Mar 28;14:1041525. doi: 10.3389/fimmu.2023.1041525. eCollection 2023.
BACKGROUND
Treatment of ER breast cancer with intramuscular formulation of Formestane (4-OHA) shrinks the tumor within weeks. Since the tedious way of intramuscular administration and side effects are not suited for adjuvant treatment, Formestane was withdrawn from the market. A new transdermal formulation of 4-OHA cream may overcome the defects and retain the effect of shrinking the breast cancer tumor. However, the effects of 4-OHA cream on breast cancer need further confirmatory studies.
METHODS
In this work, , the influence of 4-OHA cream on breast cancer was evaluated using the mode of 7,12-dimethylbenz(a)anthracene (DMBA) induced rat mammary cancer. We explored the common molecule mechanisms of action of 4-OHA cream and its injection formulation on breast cancer through RNA- sequencing-based transcriptome analysis and several biochemical experiments.
RESULTS
The results showed that the cream substantially reduced the entire quantity, size, and volum of tumors in DMBA-treated rats consistent with 4-OHA injection, and indicated that there were comprehensive signals involved in 4-OHA antitumor activity, such as ECM-receptor interaction, focal adhesion, PI3K-Akt signaling pathway, and proteoglycans in cancer. In addition, we observed that both 4-OHA formulations could enhance immune infiltration, especially CD8 T cells, B cells, natural killer cells, and macrophages infiltration, in the DMBA-induced mammary tumor tissues. The antitumor effects of 4-OHA partly depended on these immune cells.
CONCLUSION
4-OHA cream could inhibit breast cancer growth as its injection formulation and may provide a new way for neoadjuvant treatment of ER breast cancer.
背景
肌肉注射 Formestane（4-OHA）制剂治疗 ER 型乳腺癌可在数周内使肿瘤缩小。由于肌肉注射的繁琐方式和副作用不适合辅助治疗，Formestane 已从市场上撤出。4-OHA 的新型透皮乳膏制剂可能克服这些缺陷并保留缩小乳腺癌肿瘤的效果。然而，4-OHA 乳膏对乳腺癌的作用仍需进一步的确认性研究。
方法
在这项工作中，我们使用 7,12-二甲基苯并(a)蒽（DMBA）诱导的大鼠乳腺癌模型评估了 4-OHA 乳膏对乳腺癌的影响。我们通过 RNA 测序转录组分析和几种生化实验，探讨了 4-OHA 乳膏与其注射制剂对乳腺癌的共同分子作用机制。
结果
结果表明，乳膏制剂可显著减少 DMBA 处理大鼠的肿瘤总数量、大小和体积，与 4-OHA 注射剂的效果一致，这表明 4-OHA 具有广泛的抗肿瘤活性信号，如细胞外基质-受体相互作用、焦点黏附、PI3K-Akt 信号通路和癌症中的蛋白聚糖。此外，我们观察到两种 4-OHA 制剂均可增强 DMBA 诱导的乳腺肿瘤组织中的免疫浸润，特别是 CD8+T 细胞、B 细胞、自然杀伤细胞和巨噬细胞浸润。4-OHA 的抗肿瘤作用部分依赖于这些免疫细胞。
结论
4-OHA 乳膏可以抑制乳腺癌的生长，与注射制剂效果相当，为 ER 型乳腺癌的新辅助治疗提供了一种新方法。
Zotero 插件