Enhancing anti-tumor effect of I-131 MIBG therapy for neuroblastoma by inhibition of cell recovery

I-131间碘苄基胍(MIBG)已用于治疗高危神经母细胞瘤患者。I-131MIBG在肿瘤细胞内蓄积，经高能β射线照射后具有抗肿瘤作用。咖啡因属于嘌呤类生物碱，通过抑制DNA修复而在肿瘤细胞中发挥抗肿瘤作用。本研究探讨I-131MIBG与咖啡因对人神经母细胞瘤细胞株SK-N-SH的作用。细胞用浓度高达40 mM的咖啡因处理，咖啡因的抗肿瘤作用呈浓度依赖性。然而，咖啡因处理的神经母细胞瘤细胞对I-131MIBG的摄取减少，与负荷时间无关。这些结果表明，大剂量咖啡因具有抗肿瘤作用，但I-131MIBG与咖啡因联合应用的抗肿瘤作用不会增强，可能是通过减少对I-131MIBG的摄取来实现的。

I-131 meta-iodobenzylguanidine (MIBG) has been used to treat patients with high-risk neuroblastoma. I-131 MIBG accumulate into tumor cells and has an anti-tumor effect by high-energy beta-irradiation. Caffeine is classified as purine alkaloids, and has anti-tumor effect in tumor cells by inhibition of DNA-repair. This study was performed whether I-131 MIBG interacted with caffeine for human neuroblastoma cell line SK-N-SH. Cells were treated with caffeine at concentrations as high as 40 mM, and the anti-tumor effect of caffeine was concentrate-dependent. However, uptake of I-131 MIBG into neuroblastoma cells treated by caffeine was reduced independently of the load timing. These results suggest that high-dose caffeine has anti-tumor effect, but the anti-tumor effect by combined I-131 MIBG and caffeine will not be enhanced, probably by decreasing uptake of I-131 MIBG.