PO.CL07.05 · 临床研究
针对炎性乳腺癌中Lipocalin-2的小分子抑制剂表征
Characterization of small molecule inhibitors against Lipocalin-2 in inflammatory breast cancer
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
炎性乳腺癌（IBC）是一种罕见且极具侵袭性的乳腺癌（BC）类型，其癌细胞会阻塞皮肤中的淋巴管。它仅占所有乳腺癌的约1%至5%，但其生长和扩散速度远快于其他常见的BC类型。目前尚无针对IBC的靶向治疗。Lipocalin 2（LCN2）是一种分泌型糖蛋白，参与小分子亲脂性配体的转运，其异常表达在IBC的进展和转移中起重要作用。我们使用了一个包含370,000个小分子抑制剂（SMI）的文库，经生物信息学和筛选分析后，选出了24个可能与LCN2结合的化合物。我们在IBC细胞系SUM-149上进行了活力和集落形成实验。24个SMI中的大多数未表现出对细胞活力的明显降低。然而，在1.0 µM浓度下，有12个SMI使细胞增殖降低超过50%。这些结果凸显了SMI针对LCN2的治疗潜力和选择性。用我们的SMI靶向该蛋白可能提供一种新的治疗策略，改善IBC患者的预后。仍需进一步研究以验证和优化最有效的化合物，用于未来的临床开发。
查看英文原文 English abstract
Inflammatory breast cancer (IBC) is a rare and very aggressive form of breast cancer (BC) where cancer cells block the lymph vessels in the skin. It only makes up about 1% to 5% of all breast cancers but grows and spreads much faster than other common BC types. No targeted therapies are currently available against IBC. Lipocalin 2 (LCN2) is a secreted glycoprotein involved in transporting small lipophilic ligands, and its abnormal expression plays an important role in the progression and metastasis of IBC. We used a library of 370,000 small molecule inhibitors (SMI) and after bioinformatic and filtering analysis we selected 24 compounds that potentially bind to LCN2. Viability and colony formation assay were performed on the IBC cell line, SUM-149. The majority of the 24 SMIs did not exhibited noticeable reduction on cell viability. However, at 1.0 µM, 12 SMIs achieved >50% reduction in cell proliferation. These results highlight the therapeutic potential and selectivity of SMIs against LCN2. Targeting this protein with our SMIs could provide a novel therapeutic strategy that improves the outcomes of IBC patients. Further studies are needed to validate and optimize the most effective compounds for future clinical development.
利益披露 Disclosure
S. Estrada-Mojica, None..
F. Valiyeva, None.