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.