Photodynamic Therapy (PDT) is an emerging method to treat colorectal cancers (CRC). Hypericin (HYP) is an effective mediator of PDT and the ABCG2 inhibitor, Febuxostat (FBX) could augment PDT. HT29 and HEK293 cells showed light dependant cytotoxic response to PDT in both 2D and 3D cell models. FBX co-treatment was not found to improve PDT cytotoxicity. Next, ABCG2 protein expression was observed in HT29 but not in HEK293 cells. However, ABCG2 gene expression analysis did not support protein expression results as ABCG2 gene expression results were found to be higher in HEK293 cells. Although HYP treatment was found to significantly reduce ABCG2 gene expression levels in both cell lines, FBX treatment partially restored ABCG2 gene expression. Our findings indicate that FBX co-treatment may not be suitable for augmenting HYP-mediated PDT in CRC but could potentially be useful for other applications.

Graphical Abstract

中文翻译：

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非布索坦在 ABCG2 表达中的矛盾作用与增强金丝桃素介导的结直肠癌光动力治疗的矛盾作用

光动力疗法（PDT）是一种治疗结直肠癌（CRC）的新兴方法。金丝桃素 (HYP) 是 PDT 的有效介质，ABCG2 抑制剂非布索坦 (FBX) 可以增强 PDT。 HT29 和 HEK293 细胞在 2D 和 3D 细胞模型中均表现出对 PDT 的光依赖性细胞毒性反应。未发现 FBX 联合治疗可改善 PDT 细胞毒性。接下来，在 HT29 细胞中观察到 ABCG2 蛋白表达，但在 HEK293 细胞中未观察到。然而，ABCG2基因表达分析并不支持蛋白质表达结果，因为发现 HEK293 细胞中ABCG2基因表达结果较高。尽管发现 HYP 处理显着降低了两种细胞系中的ABCG2基因表达水平，但 FBX 处理部分恢复了ABCG2基因表达。我们的研究结果表明，FBX 联合治疗可能不适合增强 CRC 中 HYP 介导的 PDT，但可能对其他应用有用。

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