Development of novel lead compounds with enhancing effect on ALA-based photodynamic therapy

使用5-氨基乙酰丙酸的原卟啉IX（PpIX）依赖性光动力学诊断（PDD）和治疗（PDT）ALA-PDD和ALA-PDT是广泛认可的用于治疗各种癌症的新型治疗策略。我们证明了ALA通过转运蛋白PEPT 1的流入和胞内PpIX通过ABC转运蛋白ABCG 2的流出之间的平衡决定了癌细胞对ALA的敏感性。PDT。最近，我们发现席夫碱衍生物TX-816可以显著增强ALA-PDT的效应。TX-816增强ALA-PDT疗效的能力明显强于抑制ABCG 2和平衡核苷转运蛋白的双嘧达莫。此外，TX-816可以恢复具有获得性耐药的癌细胞对ALA-PDT的敏感性。这些结果表明TX-816是开发ALA-PDT敏化剂的有效先导化合物。

Protoporphyrin IX (PpIX)-dependent photodynamic diagnosis (PDD) and therapy (PDT) using 5-aminolevulinic acid (ALA-PDD and ALA-PDT) are widely recognized novel therapeutic strategies for the treatment of various cancers.Previously, we demonstrated that the balance between the influx of ALA through the transporter PEPT1 and the efflux of intracellular PpIX through the ABC transporter ABCG2 determines the sensitivity of cancer cells to ALA-PDT. Recently, we found that the Schiff base derivative TX-816 could significantly increase the effect of ALA-PDT. The ability of TX-816 to enhance the efficacy of ALA-PDT was markedly stronger than that of dipyridamole, which inhibits ABCG2 and equilibrative nucleoside transporters. Furthermore, TX-816 could recover the sensitivity to ALA-PDT in cancer cells with acquired resistance. These results indicate TX-816 is a potent lead compound to develop an ALA-PDT sensitizer.