FAAH inhibition ameliorates breast cancer in a murine model.
FAAH inhibition ameliorates breast cancer in a murine model.
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DOI：
10.18632/oncotarget.28534
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发表时间：
2023-10-31
期刊：
影响因子：
--
通讯作者：
Mohan, Chandra
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文献类型：
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作者：
Tripathy, Mallika;Bui, Amy;Henderson, Jared;Sun, Jeffrey;Woods, Christian Rutan;Somani, Soumya;Doan, Thao;Louis Sam Titus, Anto Sam Crosslee;Mohan, Chandra
乳腺癌是全世界女性的主要癌症。疾病结果取决于癌症的激素状态以及癌症是否转移，但在一线治疗失败的情况下需要更有效的治疗策略。在这项研究中，脂肪酸酰胺水解酶（FAAH）抑制和内源性大麻素作为治疗替代方案进行了检查。 FAAH 是一种内在膜酶，可水解内源性大麻素，使其失去活性，并且抑制 FAAH 预计会增加癌细胞死亡。为了测试这一点，使用蛋白质印迹分析来探测乳腺癌细胞的 FAAH 表达，并用 FAAH 抑制剂、外源性内源性大麻素以及两种治疗的组合进行处理，并评估其活力。在不同的乳腺癌细胞系中观察到高水平的 FAAH。 FAAH抑制比外源性内源性大麻素治疗更有效，并且FAAH抑制剂与内源性大麻素联合在体外诱导乳腺癌细胞凋亡最有效。此外，体内 FAAH 抑制可减少免疫缺陷小鼠的乳腺癌生长。 FAAH 抑制是一种有前途的方法，该领域已经取得了巨大进展，验证了这种机制作为化疗的替代方案。有必要进一步研究探索 FAAH 表达对癌细胞的治疗潜力和影响。
Breast cancer is the leading cancer among females worldwide. Disease outcome depends on the hormonal status of the cancer and whether or not it is metastatic, but there is a need for more efficacious therapeutic strategies where first line treatment fails. In this study, Fatty Acid Amide Hydrolase (FAAH) inhibition and endocannabinoids were examined as therapeutic alternatives. FAAH is an integral membrane enzyme that hydrolyzes endocannabinoids, rendering them inactive, and FAAH inhibition is predicted to increase cancer cell death. To test this, breast cancer cells were probed for FAAH expression using Western blot analysis, treated with FAAH inhibitors, exogenous endocannabinoids, and combinations of the two treatments, and assessed for viability. High levels of FAAH were observed in different breast cancer cell lines. FAAH inhibition was more effective than exogenous endocannabinoid treatment, and the combination of FAAH inhibitors and endocannabinoids was the most effective in inducing apoptosis of breast cancer cells in vitro. In addition, in vivo FAAH inhibition reduced breast cancer growth in immunodeficient mice. FAAH inhibition is a promising approach, and tremendous progress has been made in the field to validate this mechanism as an alternative to chemotherapy. Further research exploring the therapeutic potential and impact of FAAH expression on cancer cells is warranted.