Among the most malignant cancers, oral squamous cell carcinoma (OSCC) stands out as the most common malignant head and neck tumor. Despite advances in the field of treatment, the prognosis of patients with OSCC remains poor. Aiming to overcome the limitations of the currently existing therapies against OSCC, the present work aims to investigate the potential of photodynamic therapy (PDT) with phenothiazine derivatives used alone or in combination. The incorporation of methylene blue (MB) and toluidine blue (TB) was evaluated in OSCC cell lines (HSC-3 and SCC-9) and a nontumor cell line (Hfib). Both compounds exhibited concentration and time-dependent incorporation, with higher rates observed in tumor cells. Regarding dark-phase cytotoxic activity, SCC-9 cells were the most sensitive cell line with an IC50value of 362.6 µM and 41.4 µM for MB and TB, respectively. Using PDT, all lineages showed greater sensitivity, presenting lower IC50values when compared to the dark phase values. The combination index values of 0.69 (dark phase) and 0.73 (clear phase) associated with concave isobolograms, in both phases, revealed that MB and TB have synergistic effects when combined against SCC-9 cells. These findings suggest that MB or TB assisted with PDT holds promise for OSCC treatment.
在众多高度恶性的癌症中,口腔鳞状细胞癌(OSCC)作为最常见的头颈部恶性肿瘤尤为突出。尽管治疗领域已取得进展,但OSCC患者的预后仍然较差。为克服现有OSCC治疗方法的局限性,本研究旨在探讨吩噻嗪衍生物单独或联合应用在光动力疗法(PDT)中的潜力。研究在OSCC细胞系(HSC-3和SCC-9)及非肿瘤细胞系(Hfib)中评估了亚甲蓝(MB)和甲苯胺蓝(TB)的摄取情况。两种化合物均呈现浓度和时间依赖性摄取特征,且在肿瘤细胞中表现出更高的摄取率。在暗相细胞毒性活性方面,SCC-9细胞对两种化合物最为敏感,MB和TB的IC50值分别为362.6 µM和41.4 µM。采用PDT处理后,所有细胞系均表现出更高的敏感性,其IC50值较暗相值显著降低。通过联合指数分析发现,暗相0.69与明相0.73的协同指数值,配合双相下凹型等效线图,证实MB与TB联合作用于SCC-9细胞时具有协同效应。这些研究结果表明,MB或TB辅助PDT在OSCC治疗中具有良好应用前景。