Department of Molecular Biology, Faculty of Natural Sciences, Ariel University, Ariel 4070000, Israel.
Adelson School of Medicine, Ariel University, Ariel 4070000, Israel.
Int J Mol Sci. 2021 Sep 3;22(17):9579. doi: 10.3390/ijms22179579.
We examined the effects of ALOS4, a cyclic peptide discovered previously by phage library selection against integrin αβ, on a human melanoma (A375) xenograft model to determine its abilities as a potential anti-cancer agent. We found that ALOS4 promoted healthy weight gain in A375-engrafted nude mice and reduced melanoma tumor mass and volume. Despite these positive changes, examination of the tumor tissue did not indicate any significant effects on proliferation, mitotic index, tissue vascularization, or reduction of αSMA or Ki-67 tumor markers. Modulation in overall expression of critical downstream αβ integrin factors, such as FAK and Src, as well as reductions in gene expression of and transcription factors, indirectly confirmed our suspicions that ALOS4 is likely acting through an integrin-mediated pathway. Further, we found no overt formulation issues with ALOS4 regarding interaction with standard inert laboratory materials (polypropylene, borosilicate glass) or with pH and temperature stability under prolonged storage. Collectively, ALOS4 appears to be safe, chemically stable, and produces anti-cancer effects in a human xenograft model of melanoma. We believe these results suggest a role for ALOS4 in an integrin-mediated pathway in exerting its anti-cancer effects possibly through immune response modulation.
我们研究了先前通过噬菌体文库筛选针对整合素 αβ 发现的环状肽 ALOS4 对人黑色素瘤（A375）异种移植模型的影响，以确定其作为潜在抗癌药物的能力。我们发现 ALOS4 促进了 A375 植入裸鼠的健康体重增加，并减少了黑色素瘤肿瘤的质量和体积。尽管这些变化是积极的，但对肿瘤组织的检查并未表明对增殖、有丝分裂指数、组织血管生成或减少 αSMA 或 Ki-67 肿瘤标志物有任何显著影响。关键下游 αβ 整合素因子的总体表达的调节，如 FAK 和 Src，以及转录因子和 的基因表达减少，间接证实了我们的怀疑，即 ALOS4 可能通过整合素介导的途径发挥作用。此外，我们发现 ALOS4 与标准惰性实验室材料（聚丙烯、硼硅酸盐玻璃）或在长时间储存下的 pH 值和温度稳定性之间没有明显的配方问题。总的来说，ALOS4 似乎是安全的，化学稳定的，并在人黑色素瘤异种移植模型中产生抗癌作用。我们认为这些结果表明 ALOS4 在整合素介导的途径中发挥作用，可能通过免疫反应调节发挥其抗癌作用。
