Development of photodynamic therapy targeted at glioma stem cells

针对神经胶质瘤干细胞的光动力疗法的发展

• 批准号: 23592147
• 负责人: KUROIWA Toshihiko
• 金额: $ 3.24万
• 依托单位: Osaka Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23592147/
• 关键词: 光線力学治療; 5－アミノレブリン酸; ポルフィリン; 脳腫瘍; 悪性グリオーマ; がん幹細胞; ABCG2; 光線力学診断; チロシンキナーゼ阻害薬; 悪性脳腫瘍; 光線力学療法; 5アミノレブリン酸; ５アミノレブリン酸

Cancer stem cells is a main cause of resistance of various cancer therapies. ABCG2 transporter, which is highly express in cancer stem cells, also transport excessive porphyrin to extra-cellular space. Therefore, controlling ABCG2 may enhance the effect of 5-ALA PDT and may control cancer stem cells.In this study, we found that more than a half of porphyrin by produced by 5-ALA administration transported to extracellular space, and inhibition of ABCG2 transporter increased intra-cellular porphyrin and enhanced 5-ALA PDT effect. Furthermore, A172 glioma stem cell had a nature of 5-ALA PDT sensitivity, rather than resistance. These results indicated that 5-ALA PDT and/or combined with ABCG2 inhibitor may useful for controlling the cancer stem cells.

癌症干细胞是各种癌症治疗耐药的主要原因。ABCG 2转运蛋白在肿瘤干细胞中高度表达，也将过量的卟啉转运到细胞外空间。因此，控制ABCG 2可以增强5-ALA PDT的效果，并可能控制癌症干细胞。在本研究中，我们发现，超过一半的卟啉通过5-ALA给药产生转运到细胞外空间，和ABCG 2转运蛋白的抑制增加细胞内卟啉和增强5-ALA PDT的效果。此外，A172胶质瘤干细胞对5-ALA PDT具有敏感性，而非抵抗性。这些结果表明，5-ALA PDT和/或联合ABCG 2抑制剂可能有助于控制肿瘤干细胞。