Development of novel PDT with glucose-conjugated chlorin for gastric cancer and GIST

胃肠道间质瘤(GIST)除手术切除外，尚无有效的治疗策略。光动力疗法(PDT)包括静脉注射光敏剂，该光敏剂由特定波长的光激活，产生可直接杀死肿瘤细胞的活性氧物种。我们使用一种新开发的光敏剂--葡萄糖结合氯(G-氯)来分析光动力疗法治疗胃肠道间质瘤的疗效。在体外，GIST-T1细胞葡萄糖转运体GLUT1、GLUT3和GLUT4的表达、细胞对G-氯的摄取以及光动力疗法介导的G-氯诱导的细胞凋亡均显著高于WI-38细胞。在体内，GIST-T1细胞移植瘤中G-氯蓄积高于邻近正常组织，肿瘤生长在PDT后明显受到抑制。

Except for surgical resection, no effective treatment strategies have been established for gastrointestinal stromal tumors (GISTs). Photodynamic therapy (PDT) consists of intravenous administration of a photosensitizer, activated by a specific wavelength of light, which produces reactive oxygen species that directly kill tumor cells. We analyzed the efficacy of PDT using a newly developed photosensitizer, glucose-conjugated chlorin (G-chlorin) for the GIST treatment. In vitro, the expression of the glucose transporters GLUT1, GLUT3, and GLUT4, the cellular uptake of G-chlorin, and apoptosis mediated by PDT with G-chlorin were significantly higher in GIST-T1 than in WI-38 cells. In vivo, G-chlorin accumulation was higher in xenograft tumors of GIST-T1 cells than in the adjacent normal tissue, and tumor growth was significantly suppressed following PDT.