Moayed Fuad, Keil Silvia, Dittmar Thomas, Weiler Julian
Institute of Immunology, Center for Biomedical Education and Research (ZBAF), Witten/Herdecke University, Stockumer Str. 10, Witten, Germany.
Mol Biol Rep. 2025 Jun 5;52(1):553. doi: 10.1007/s11033-025-10666-1.
The antibiotic minocycline has been suggested as a potential agent in cancer therapy due to its anti-inflammatory properties and effectiveness as an NF-κB inhibitor. In previous studies, we showed that minocycline could effectively block the fusion of breast epithelial cells and cancer cells. However, its influence on breast cancer cell characteristics, including proliferation, migration, and gene expression has not yet been investigated.
M13SV1-EGFP-Neo breast epithelial cells, HS578T-Hyg breast cancer cells and M13HS-2 and M13HS-8 tumor hybrids were used as breast (cancer) model cell lines in this study. Cells were treated with up to 50 µg/ml minocycline. An XTT assay and a colony formation assay were used to study cell proliferation. Western blot analysis and Zymography were used to examine the expression of MMP-2 and MMP-9, EMT, and stemness marker. Cell migration was measured by Scratch assay. Using a two-way ANOVA and the Tukey post-hoc test, statistical significance was determined.
Minocycline inhibited proliferation and colony formation capacity in a dose-dependent manner, whereas EMT and stemness marker expression remained unchanged in all cell lines. Zymography data showed that MMP-2 and MMP-9 expression was down-regulated M13SV1-EGFP-Neo treated with minocycline, but not in HS578T-Hyg cells or M13HS-2 and M13HS-8 tumor hybrids. Minocycline inhibited the migration of M13SV1-EGFP-Neo cells in a dose-dependent manner, while the migration of HS578T-Hyg, M13HS-2 and M13HS-8 tumor hybrid cells necessitated a minimum of 25 µg/ml minocycline, CONCLUSIONS: The results showed that non-malignant cells and neoplastic cells reacted differently to minocycline. This could mean that minocycline will have unwanted side effects if it is used in cancer therapy.
由于抗生素米诺环素具有抗炎特性且作为核因子κB抑制剂有效，因此被认为是癌症治疗中的一种潜在药物。在先前的研究中，我们表明米诺环素可有效阻断乳腺上皮细胞与癌细胞的融合。然而，其对乳腺癌细胞特性（包括增殖、迁移和基因表达）的影响尚未得到研究。
在本研究中，使用M13SV1-EGFP-Neo乳腺上皮细胞、HS578T-Hyg乳腺癌细胞以及M13HS-2和M13HS-8肿瘤杂交细胞作为乳腺（癌）模型细胞系。细胞用高达50µg/ml的米诺环素处理。采用XTT法和集落形成试验研究细胞增殖。蛋白质免疫印迹分析和酶谱分析用于检测基质金属蛋白酶-2（MMP-2）和基质金属蛋白酶-9（MMP-9）的表达、上皮-间质转化（EMT）以及干性标志物。通过划痕试验测量细胞迁移。使用双向方差分析和Tukey事后检验确定统计学显著性。
米诺环素以剂量依赖方式抑制增殖和集落形成能力，而所有细胞系中的EMT和干性标志物表达均保持不变。酶谱数据显示，用米诺环素处理的M13SV1-EGFP-Neo中MMP-2和MMP-9表达下调，但在HS578T-Hyg细胞或M13HS-2和M13HS-8肿瘤杂交细胞中未下调。米诺环素以剂量依赖方式抑制M13SV1-EGFP-Neo细胞的迁移，而HS578T-Hyg、M13HS-2和M13HS-8肿瘤杂交细胞的迁移至少需要25µg/ml的米诺环素。
结果表明，非恶性细胞和肿瘤细胞对米诺环素的反应不同。这可能意味着米诺环素用于癌症治疗时会产生不良副作用。
