CBIOS, Universidade Lusófona Research Center for Biosciences & Health Technologies, Campo Grande 376, Lisboa 1749-024, Portugal; Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, Lisboa 1649-003, Portugal.
CBIOS, Universidade Lusófona Research Center for Biosciences & Health Technologies, Campo Grande 376, Lisboa 1749-024, Portugal.
Redox Biol. 2019 Jan;20:367-378. doi: 10.1016/j.redox.2018.10.016. Epub 2018 Oct 25.
Manganese(III) porphyrins (MnPs) are superoxide dismutase (SOD) mimics with demonstrated beneficial effects in cancer treatment in combination with chemo- and radiotherapy regimens. Despite the ongoing clinical trials, little is known about the effect of MnPs on metastasis, being therefore essential to understand how MnPs affect this process. In the present work, the impact of the MnP MnTnHex-2-PyP in metastasis-related processes was assessed in breast cancer cells (MCF-7 and MDA-MB-231), alone or in combination with doxorubicin (dox). The co-treatment of cells with non-cytotoxic concentrations of MnP and dox altered intracellular ROS, increasing HO. While MnP alone did not modify cell migration, the co-exposure led to a reduction in collective cell migration and chemotaxis. In addition, the MnP reduced the dox-induced increase in random migration of MDA-MB-231 cells. Treatment with either MnP or dox decreased the proteolytic invasion of MDA-MB-231 cells, although the effect was more pronounced upon co-exposure with both compounds. Moreover, to explore the cellular mechanisms underlying the observed effects, cell adhesion, spreading, focal adhesions, and NF-κB activation were also studied. Although differential effects were observed according to the endpoints analysed, overall, the alterations induced by MnP in dox-treated cells were consistent with a therapeutically favorable outcome.
锰(III)卟啉（MnPs）是一种超氧化物歧化酶（SOD）模拟物，已被证明在与化疗和放疗联合治疗癌症方面具有有益的效果。尽管正在进行临床试验，但对于 MnPs 对转移的影响知之甚少，因此了解 MnPs 如何影响这一过程至关重要。在本工作中，评估了 MnP MnTnHex-2-PyP 对乳腺癌细胞（MCF-7 和 MDA-MB-231）中转移相关过程的影响，单独或与多柔比星（dox）联合使用。用非细胞毒性浓度的 MnP 和 dox 共同处理细胞会改变细胞内的 ROS，增加 HO。虽然 MnP 本身不会改变细胞迁移，但共同暴露会导致细胞集体迁移和趋化性减少。此外，MnP 减少了 dox 诱导的 MDA-MB-231 细胞随机迁移的增加。用 MnP 或 dox 处理均可减少 MDA-MB-231 细胞的蛋白水解侵袭，尽管当两种化合物同时暴露时，效果更为明显。此外，为了探讨观察到的效应的细胞机制，还研究了细胞黏附、铺展、焦点黏附和 NF-κB 激活。尽管根据分析的终点观察到了不同的效应，但总的来说，MnP 在 dox 处理的细胞中诱导的改变与治疗上有利的结果一致。
