苯丁酸钠诱导分化治疗可移植性人脑胶质瘤实验研究

Experimental research of differentiation-inducing therapy on human glioma xenograft by sodium phenylbutyrate

目的 探讨诱导分化剂苯丁酸钠与化疗药顺铂联合治疗可移植性人脑胶质瘤的剂量及疗效。方法 将低分化人脑胶质瘤体外细胞系SHG-44-9移植于裸小鼠,制作可移植性实体瘤模型后,用不同剂量的苯丁酸钠单独或与顺铂联合治疗,观察实体瘤的体积、组织细胞形态和胶质纤维酸性蛋白表达量的变化。结果 当苯丁酸钠增加至300mg·kg-1,每天2次腹腔注射时,肿瘤生长明显受抑（P<0.001）,组织细胞形态和胶质纤维酸性蛋白表达与对照组相比显示其分化程度增高,但与顺铂联用未显示出疗效的增加。结论 苯丁酸钠具有明显的促进人脑胶质瘤细胞分化的作用。

Objective To observe the effect and the dosages of combined application of sodium phenylbutyrate (SPB, a differentiation-inducing agent ) and cisplatin ( a chemotherapeutic agent) on human glioma xenograft model. Methods Low differentiation human glioma cell line SHG-44-9 was inoculated subcutaneously into the NC athymic nude mice to establish a human glioma xenograft tumor model. Then the tumor-bearing mice were treated by SPB alone in various dosages or combined with cisplatin. Changes in tumor volumes, histomorphology and the expression levels of glial fibrillary acidic protein(GFAP) of tumors were observed. Results The growth of tumors was inhibited significantly when the dosage of SPB reached 300 mg· kg-1 twice a day peritoneally (P<0.001). Histomorphology and GFAP expression showed that the differentiation degree of tumor cells increased as compared with that of the control group. However, SPB combined with cispatin showed no synergetic effect. Conclusion SPB has a significant differentiation-inducing effect on human glioma xenograft, and can be used in clinical trials.