羟基喜树碱的鼻咽癌治疗方案实验性探讨

Experimental Study on Hydroxycampothecin Therapy for Nasopharyngeal Cancer

【目的】探讨以拓扑异构酶Ⅰ抑制剂羟基喜树碱 (HCPT)为基础的治鼻咽癌联合方案。【方法】实验采用人鼻咽癌 (NPC)细胞株SUNE1,体外细胞毒测定用MTT法 ,体内实验采用SUNE1裸鼠移植瘤模型 ,研究HCPT与顺铂 (DDP)或(和 ) 5 氟尿嘧啶 (5 FU)联合用药方案的抗瘤效果。【结果】在体外实验中 ,HCPT、DDP和 5 FU单用对SUNE1的IC50 分别为3 3、2 8、8 6 μmol/L ;HCPT、DDP和 5 FU在 1∶1∶2的剂量比例合用的条件下 ,HCPT与DDP或 (和 ) 5 FU合用均具有明显的协同抗NPC作用。体内实验也表明HCPT与DDP合用具有协同抗NPC作用 (P <0 0 1) ,HPC与 5 FU合用未见明显的相加或协同作用 ,HCPT与DDP及 5 FU合用抗NPC效果较单药和两药合用为优。【结论】HCPT +DDP和HCPT +DDP +5 FU具有协同抗NPC作用。

To investigate the topoisomerase Ⅰ inhibitor 10 hydroxycampothecin based chemo therapy for nasopharyngeal cancer(NPC). The anticancer effect of 10 hydroxycampothecin (HCPT) in with 5 fluorouracil (5 FU) and/or cisplatin (DDP) were evaluated by MTT assay in vitro and by using the model of human NPC (SUNE1) xenograft in nude mice in vivo. In vitro, HCPT, 5 FU and DDP had potent cytotoxicity to SUNE1 cells, their IC 50 were 3 3 μmol/L, 8 6 mmol/L, 2 8 mmol/L, respectively, and, in the dose rate of HCPT∶DDP∶5 FU=1∶1∶2, HCPT in combination with DDP or/and 5 FU had synergistic effect. In vivo, HCPT in combination with DDP had synergistic anticancer effect(P<0 01), additivity or synergism was not observed in the combination of HCPT and 5 FU, the anticancer effect of HCPT+DDP+5FU was better than single drug and 2 drug combination. [Conclusion] HCPT+DDP and HCPT+DDP+5 FU possess synergistic effect against NPC.