苯醋酸抗脑胶质瘤颅内移植实验研究

Experimental Study of Phenylacetate against Malignant Gliomas Inoculated into Mice Brain

目的：通过苯醋酸对脑胶质瘤小鼠模型的诱导治疗，观察治疗后肿瘤细胞的变化，以评估其在体内治疗恶性脑肿瘤的效果。方法：将Ｇ４２２鼠脑胶质瘤细胞移植到昆明鼠（ｎ＝８０）脑内，并将其平均分为５组。其中３组为苯醋酸钠用药组，分别用１２００、８００、４００ｍｇ·ｋｇ１·ｄ１，自移植后的当天开始用药，连续用药１４ｄ；对照组用同样的方法注射等量的盐水；另一组为卡氮芥（ＢＣＮＵ）组，２０ｍｇ·ｋｇ１仅１次注射。治疗结束后处死小鼠，行病理、电镜和毒性观察以及流式细胞仪检查，以确定肿瘤细胞的增殖状态。结果：用苯醋酸治疗的小鼠生存期均有延长（Ｐ＜０．０５），而没有反应。ＢＣＮＵ组的生命延长期和用苯醋酸治疗的中剂量组相同。病理和电镜观察显示：用苯醋酸处理的小鼠肿瘤细胞有明显的细胞肥大和粗面内质网的机化，表示有细胞的分化。流式细胞仪检测显示，苯醋酸可以使Ｇ４２２细胞的分化阻滞在Ｇ１期。结论：醋酸钠通过抑制蛋白的戊乙烯化或其它机制，而达到抑制肿瘤细胞增殖和诱导分化的作用，可以作为治疗恶性胶质瘤或其它恶性肿瘤的安全有效的新药。

bjective: Phenylacetate can suppress the growth of tumor and induce cell differentiation in vitro.The objective of this study was to evaluate the potential antitumor efficacy of sodium phenylacetate(NaPA). Methods: Kunming mice (n=80) bearing cerebral G422 malignant gliomas,which were equally divided into five groups,were used in this experiment.Three groups were treated with different dosage of NaPA(1200,800,400mgkg1) by s.c. for 14 days from the inoculation day.Control group was treated in the same manner with normal saline.Another group was treated with bischloronitrosourea (BCNU) (20 mgkg1) once a day.Then mice were sacrificed to study the pathological and ultrastructural alterations of the tumor cells and the toxicity of NaPA.Flow cytometry (FCM) was used to investigate the proliferation of the tumor cells. Results: Treatment with NaPA can extend the survival period of the mice (P<0.05) without any associated adverse effects.The therapeutic effects of BCNU group are similar to those of the NaPA in the middle dosage group.The pathology and ultrastructure of the tumor cells after treatment have shown marked hypertrophy and organization of rough endoplasmic reticulum,indicating the differentiation of tumor cells,in contrast with the scare and randomly distributed endoplasmic reticulum in untreated tumor cells.The result of FCM showed that phenylacetate can induce cytostasis of G422 cells at the G1 phase of the cell cycle. Conclusion: Phenylacetate,acting through inhibition of protein prenylation and other mechanisms,can offer a safer and more effective approach to treat the malignant gliomas and,perhaps,other neoplasms as well.