CAJ | 학술논문

目的番荔枝内酯单体89-2是自阿蒂莫耶番荔枝植物分离获得.本研究旨在探讨89-2对MDR肿瘤的实验治疗作用.方法以MTT法测定细胞毒;KBv200及KB细胞裸鼠移植瘤模型研究89-2对MDR肿瘤的实验治疗作用;以Fura-2-AM法测定P-糖蛋白(P-gp)功能.结果 89-2对KBv200及KB细胞的IC50分别为48.7和64.6 nmol*L-1(P>0.05).89-2对KB及KBv200细胞裸鼠移植瘤具有相似的剂量依赖性抑制作用,而毒性可以耐受.89-2剂量依赖性地增加KBv200细胞的Fura-2积累.结论 89-2体内外均抑制KB和KBv200细胞生长,具有开发前景.
목적번려지내지단체89-2시자아체막야번려지식물분리획득.본연구지재탐토89-2대MDR종류적실험치료작용.방법이MTT법측정세포독;KBv200급KB세포라서이식류모형연구89-2대MDR종류적실험치료작용;이Fura-2-AM법측정P-당단백(P-gp)공능.결과 89-2대KBv200급KB세포적IC50분별위48.7화64.6 nmol*L-1(P>0.05).89-2대KB급KBv200세포라서이식류구유상사적제량의뢰성억제작용,이독성가이내수.89-2제량의뢰성지증가KBv200세포적Fura-2적루.결론 89-2체내외균억제KB화KBv200세포생장,구유개발전경.
Aim Annonaceous acetogenin 89-2 was obtained from atemoya plant. To investigate the effect of 89-2 on experimental chemotherapy against xenografts derived from multidrug resistant KBv200 cells and parental drug-sensitive KB cells. Methods Cytotoxicity was determined by tetrazolium (MTT) assay. The models of KB and KBv200 xenografts in nude mice were established to investigate the effect of 89-2 on experimental chemotherapy against cancer in vivo. Mechanistic experiments were conducted to examine the function of P-gp by Fura 2-AM assay. Results The compound 89-2 showed potent cytotoxicity in KBv200 and KB cells, and the mean IC50 of 89-2 to KBv200 and KB cells was 48.7 and 64.6 nmol*L-1, respectively. The IC50 of 89-2 to multidrug resistant (MDR) cells was similar to that to the parental drug-sensitive cells (P<0.05). In the models of KBv200 and KB cell xenografts in nude mice, 89-2 (0.90 mg*kg-1, q2d×6) exhibited 52.3% and 56.5% in inhibiting the growth of xenografts, respectively. The toxicity was endurable. The intracellular accumulation of Fura-2 in KBv200 cells increased to 1.66, 2.03, and 2.74-fold, respectively, by addition of 12.8, 64 and 320 nmol*L-1 of 89-2. Conclusion Both MDR KBv200 cells and parental drug-sensitive KB cells were sensitive to the treatment of 89-2 in vitro and in vivo. The mechanism of overcoming MDR was associated with the decrease of P-gp function MDR cells.