The contradictory role of febuxostat in ABCG2 expression and potentiating hypericin-mediated photodynamic therapy in colorectal cancers

IF 2.7 3区化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Photochemical & Photobiological Sciences Pub Date : 2024-04-16 DOI:10.1007/s43630-024-00575-w

Aaron King, Thomas Maisey, Erica L. Harris, James A. Poulter, David G. Jayne, M. Ibrahim Khot

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Abstract

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.

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非布索坦在结直肠癌 ABCG2 表达和增效金丝桃素介导的光动力疗法中的矛盾作用

光动力疗法（PDT）是治疗结直肠癌（CRC）的一种新兴方法。金丝桃素（HYP）是光动力疗法的有效介质，而ABCG2抑制剂非布索坦（FBX）可以增强光动力疗法。在二维和三维细胞模型中，HT29和HEK293细胞对PDT表现出光依赖性细胞毒性反应。发现 FBX 联合治疗并不能提高 PDT 的细胞毒性。接着，在 HT29 细胞中观察到 ABCG2 蛋白表达，但在 HEK293 细胞中没有观察到。然而，ABCG2 基因表达分析并不支持蛋白表达结果，因为在 HEK293 细胞中 ABCG2 基因表达结果更高。虽然发现 HYP 处理能显著降低两种细胞系中 ABCG2 基因的表达水平，但 FBX 处理能部分恢复 ABCG2 基因的表达。我们的研究结果表明，FBX 联合治疗可能不适合增强 HYP 介导的 PDT 在 CRC 中的作用，但有可能在其他应用中发挥作用。

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