Department of Orthopedics and Trauma Surgery, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany.
Department of Urology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany.
Int J Mol Sci. 2024 Apr 29;25(9):4868. doi: 10.3390/ijms25094868.
Non-muscle invasive bladder cancer is a common tumour in men and women. In case of resistance to the standard therapeutic agents, gemcitabine can be used as off-label instillation therapy into the bladder. To reduce potential side effects, continuous efforts are made to optimise the therapeutic potential of drugs, thereby reducing the effective dose and consequently the pharmacological burden of the medication. We recently demonstrated that it is possible to significantly increase the therapeutic efficacy of mitomycin C against a bladder carcinoma cell line by exposure to non-toxic doses of blue light (453 nm). In the present study, we investigated whether the therapeutically supportive effect of blue light can be further enhanced by the additional use of the wavelength-specific photosensitiser riboflavin. We found that the gemcitabine-induced cytotoxicity of bladder cancer cell lines (BFTC-905, SW-1710, RT-112) was significantly enhanced by non-toxic doses of blue light in the presence of riboflavin. Enhanced cytotoxicity correlated with decreased levels of mitochondrial ATP synthesis and increased lipid peroxidation was most likely the result of increased oxidative stress. Due to these properties, blue light in combination with riboflavin could represent an effective therapy option with few side effects and increase the success of local treatment of bladder cancer, whereby the dose of the chemotherapeutic agent used and thus the chemical load could be significantly reduced with similar or improved therapeutic success.
非肌肉浸润性膀胱癌是男性和女性常见的肿瘤。如果对标准治疗药物产生耐药性，可以将吉西他滨作为标签外药物用于膀胱内灌注治疗。为了减少潜在的副作用，人们一直在努力优化药物的治疗潜力，从而降低有效剂量，减少药物的药理负担。我们最近证明，通过暴露于无毒剂量的蓝光（453nm），可以显著提高丝裂霉素 C 对膀胱癌细胞系的治疗效果。在本研究中，我们研究了在使用核糖核酸的情况下，蓝光的治疗支持作用是否可以通过额外使用波长特异性光敏剂来进一步增强。我们发现，在存在核糖核酸的情况下，蓝光（非毒性剂量）可显著增强膀胱癌细胞系（BFTC-905、SW-1710、RT-112）中吉西他滨的细胞毒性。增强的细胞毒性与线粒体 ATP 合成水平降低以及脂质过氧化增加相关，这很可能是由于氧化应激增加所致。由于这些特性，蓝光与核糖核酸的联合使用可能代表一种副作用少的有效治疗选择，可以提高膀胱癌局部治疗的成功率，从而可以显著降低所用化疗药物的剂量，从而降低化学负荷，同时保持或提高治疗效果。
