Department Biomedical Engineering, University of Houston, Houston, TX 77204, USA.
Oncotarget. 2023 Oct 31;14:910-918. doi: 10.18632/oncotarget.28534.
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 addition, 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.
乳腺癌是全球女性中最常见的癌症。疾病的转归取决于癌症的激素状态以及是否发生转移，但需要更有效的治疗策略，以应对一线治疗失败的情况。在这项研究中，脂肪酸酰胺水解酶（FAAH）抑制和内源性大麻素被视为治疗的替代方法。FAAH 是一种完整的膜酶，可水解内源性大麻素，使其失去活性，而 FAAH 抑制预计会增加癌细胞死亡。为了验证这一点，使用 Western blot 分析检测了乳腺癌细胞中的 FAAH 表达，并用 FAAH 抑制剂、外源性内源性大麻素以及两种处理方法的组合对其进行了处理，并评估了其活力。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处理更有效，而 FAAH 抑制剂和内源性大麻素的组合在诱导乳腺癌细胞凋亡方面最为有效。此外，FAAH 抑制可减少免疫缺陷小鼠的乳腺癌生长。FAAH 抑制是一种很有前途的方法，该领域已经取得了巨大的进展，验证了这一机制作为化疗替代物的有效性。进一步研究 FAAH 表达对癌细胞的治疗潜力和影响是必要的。
