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比卡鲁胺增强了人源和犬源炎症性乳腺癌细胞系的体外和体内检测中的常规化疗效果。

Bicalutamide Enhances Conventional Chemotherapy in In Vitro and In Vivo Assays Using Human and Canine Inflammatory Mammary Cancer Cell Lines.

机构信息

Department Animal Physiology, Veterinary Medicine School, Complutense University of Madrid (UCM), 28040 Madrid, Spain.

Obstetrics and Gynecology Department, Hospital Clinico San Carlos, Instituto de Salud de la Mujer, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IsISSC), 28040 Madrid, Spain.

出版信息

Int J Mol Sci. 2024 Jul 19;25(14):7923. doi: 10.3390/ijms25147923.

Abstract

Human inflammatory breast cancer (IBC) and canine inflammatory mammary cancer (IMC) are highly aggressive neoplastic diseases that share numerous characteristics. In IBC and IMC, chemotherapy produces a limited pathological response and anti-androgen therapies have been of interest for breast cancer treatment. Therefore, the aim was to evaluate the effect of a therapy based on bicalutamide, a non-steroidal anti-androgen, with doxorubicin and docetaxel chemotherapy on cell proliferation, migration, tumor growth, and steroid-hormone secretion. An IMC-TN cell line, IPC-366, and an IBC-TN cell line, SUM149, were used. In vitro assays revealed that SUM149 exhibited greater sensitivity, reducing cell viability and migration with all tested drugs. In contrast, IPC-366 exhibited only significant in vitro reductions with docetaxel as a single agent or in different combinations. Decreased estrogen levels reduced in vitro tumor growth in both IMC and IBC. Curiously, doxorubicin resulted in low efficacy, especially in IMC. In addition, all drugs reduced the tumor volume in IBC and IMC by increasing intratumoral testosterone (T) levels, which have been related with reduced tumor progression. In conclusion, the addition of bicalutamide to doxorubicin and docetaxel combinations may represent a potential treatment for IMC and IBC.

摘要

人炎性乳腺癌(IBC)和犬炎性乳腺肿瘤(IMC)是具有高度侵袭性的肿瘤性疾病,具有许多共同特征。在 IBC 和 IMC 中,化疗产生的病理反应有限,而抗雄激素治疗一直是乳腺癌治疗的研究热点。因此,本研究旨在评估基于比卡鲁胺(一种非甾体类抗雄激素)联合多柔比星和多西他赛化疗治疗对细胞增殖、迁移、肿瘤生长和甾体激素分泌的影响。本研究使用了犬 IMC-TN 细胞系 IPC-366 和人 IBC-TN 细胞系 SUM149。体外实验表明,SUM149 对所有测试药物均表现出更高的敏感性,降低了细胞活力和迁移率。相比之下,IPC-366 仅在单独使用多西他赛或不同组合时表现出显著的体外抑制作用。降低雌激素水平可减少两种 IMC 和 IBC 中的体外肿瘤生长。有趣的是,多柔比星的疗效较低,特别是在 IMC 中。此外,所有药物均通过增加肿瘤内睾酮(T)水平来减少 IBC 和 IMC 的肿瘤体积,这与肿瘤进展减少有关。总之,将比卡鲁胺与多柔比星和多西他赛联合应用可能是治疗 IMC 和 IBC 的一种潜在方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/608d/11276844/3382f99cf07b/ijms-25-07923-g001.jpg

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