Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Istinye University, Istanbul, Turkey.
Department of Electric and Electronics Engineering, Faculty of Technology, Sakarya University of Applied Sciences, Sakarya, Turkey.
Lasers Med Sci. 2024 Jul 23;39(1):191. doi: 10.1007/s10103-024-04141-9.
Triple negative breast cancer (TNBC) is one of the subtypes of breast cancer characterized by a heterogeneous and aggressive nature. Photodynamic therapy (PDT) has drawn significant attention in cancer treatment. However, solubility of photosensitizer, penetration problems into a target tissue and insufficient oxygen concentration limit the effectiveness of PDT. To overcome these limitations and to reduce the side effects of chemotherapy, combination treatment modalities play an essential role in cancer treatment. In this study, we aimed to investigate the combination efficacy of cisplatin-based chemotherapy and 5-Aminolevulinic acid (5-ALA)/PDT in TNBC cells and healthy breast cells in vitro. To determine the effect of the combination effects of cisplatin and 5-ALA/PDT on TNBC cells, two treatment protocols (simultaneous and sequential combination therapy) were evaluated compared with cisplatin and 5-ALA/PDT monotherapy and WST-1, Annexin V assay, acridine orange (AO) and mitochondrial staining were performed. Our findings showed that MDA-MB-231 TNBC cell viability was significantly decreased following simultaneous combination treatment compared to cisplatin and 5-ALA/PDT monotherapy. Additionally, simultaneous combination treatment was more effective than sequential combination treatment. The simultaneous combination treatment of 2.5 µM cisplatin and 5-ALA/PDT at 6 J/cm and 9 J/cm induced 46.78% and 53.6% total apoptotic death, respectively in TNBC cells compared with monotherapies (cisplatin (37.88%) and 5-ALA/PDT (6 J/cm: 31.48% and 9 J/cm: 37.78%). Additionally, cisplatin and 5-ALA/PDT combination treatment resulted in nuclear fragmentation and mitochondrial damage due to apoptosis. Our results suggest that cisplatin and 5-ALA/PDT simultaneous combination therapy could be a promising new alternative strategy for treating TNBC. However, further studies are required to assess the underlying molecular mechanisms of cisplatin and 5-ALA/PDT combination treatment at the molecular level.
三阴性乳腺癌（TNBC）是乳腺癌的一种亚型，具有异质性和侵袭性。光动力疗法（PDT）在癌症治疗中引起了广泛关注。然而，光敏剂的溶解度、进入目标组织的渗透问题以及氧气浓度不足限制了 PDT 的效果。为了克服这些限制并减少化疗的副作用，联合治疗方法在癌症治疗中起着至关重要的作用。在这项研究中，我们旨在研究基于顺铂的化疗和 5-氨基酮戊酸（5-ALA）/PDT 在 TNBC 细胞和健康乳腺细胞中的联合疗效。为了确定顺铂和 5-ALA/PDT 联合治疗对 TNBC 细胞的影响，我们评估了两种治疗方案（同时和序贯联合治疗），并与顺铂和 5-ALA/PDT 单药治疗以及 WST-1、 Annexin V 检测、吖啶橙（AO）和线粒体染色进行了比较。我们的研究结果表明，与顺铂和 5-ALA/PDT 单药治疗相比，MDA-MB-231 TNBC 细胞的活力在同时联合治疗后显著降低。此外，同时联合治疗比序贯联合治疗更有效。与单药治疗（顺铂（37.88%）和 5-ALA/PDT（6 J/cm：31.48%和 9 J/cm：37.78%）相比，同时联合治疗 2.5 µM 顺铂和 5-ALA/PDT 分别在 6 J/cm 和 9 J/cm 时诱导 46.78%和 53.6%的总凋亡死亡。此外，顺铂和 5-ALA/PDT 联合治疗导致核片段化和线粒体损伤，从而引发凋亡。我们的结果表明，顺铂和 5-ALA/PDT 同时联合治疗可能是治疗 TNBC 的一种有前途的新策略。然而，需要进一步研究来评估顺铂和 5-ALA/PDT 联合治疗在分子水平上的潜在分子机制。
