| Malignant brain tumors (gliomas) can rarely be cured by surgery and/or radiotherapy alone. Chemotherapy, as generally available, has been of limited value. For years, researchers puzzled over an aggressive form of brain cancer. The lethal glioma tumors often outsmart traditional cancer treatments such as surgery, and quickly invade healthy brain tissue. But now an understanding of the biological makeup and survival mechanisms of glioma tumors is helping researchers develop methods that they hope will kill the cancer. Brain tumors always have been one of the most devastating diseases because they are so difficult to treat, much less cure.Phenylacetic acid (PA) is a catabolite of phenylalanine, excessively formed and excreted in the urine in phenylketonuria. An abnormal production of phenylalanine catabolism that appears in the urine in phenylketonuria. Phenylacetate is a small molecule that is a product of phenylalanine metabolism and is normally present in the mammalian circulation at very low levels. It has long been safely used in humans to treat the hyperammonemia resulting from urea synthesis disorders and liver failure. It has recently been investigated as an anticancer agent because it decreased growth and increased differentiation of a variety of human neoplasms, including prostate cancer in which a phase I trial has recently been completed.Phenylacetate has recently been shown to suppress tumor growth and promote differentiation in experimental models. A phase I trial of phenylacetate was conducted in 17 patients with advanced solid tumors. Phenylacetate, a deaminated metabolite of phenylalanine, has been implicated in damage to immature brain in phenylketonuria. Because primary brain tumors are highly reminiscent of the immature central nervous system, these neoplasms should be equally vulnerable. We show here that sodium phenylacetate can induce cytostasis and reversal of malignant properties of cultured human glioblastoma cells, when used at pharmacological concentrations that are well tolerated by children and adults. Treated tumor cells exhibited biochemical alterations similar to those observed in phenylketonuria-like conditions, including selective decline in de novo cholesterol synthesis from mevalonate. Because gliomas, but not mature normal brain cells, are highly dependent on mevalonate for production of sterols and isoprenoids vital for cell growth, sodium phenylacetate would be expected to affect tumor growth in vivo while sparing normal issues. Systemic treatment of rats bearing intracranial gliomas resulted in significant tumor suppression with no apparent toxicity to the host.The data indicate that phenylacetate, acting through inhibition of protein prenylation and other mechanisms, may offer a safe and effective novel approach to treatment of malignant gliomas and perhaps other neoplasms as well.AimsTo observe the level of HoxA group genes mRNA expression in glioma C6 cells.To observe the level of HoxA group genes mRNA expression in glioma tissues. To observe the effects of phenylacetate regulates expression of HoxA group genes mRNA in glioma C6 cells.MethodsAstrocytes of rat brain tissue were primarily cultured and C6 cells were cultured in vitro. The expression of HoxA group genes mRNA before and after treated by phenylacerate were detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) in the presence of specific primers. The level of Hox gene expression was expressed as ratio expression rate (RER) of Hox gene /β-actin according to Computer Image analysis and the difference between C6 cells and rat brain tissue cells was analyzed by student t-test.ResultsH0XA1, A2, A4 and A10 genes expression levels in glioma C6 cells were significantly higher than in rat brain tissue.HOXA2, A4, A6, A7, A9, A10 genes expression levels in glioma tissus were significantly higher than in human brain tissue.HOXA4, A10 genes high level expression in glioma tissus hasn't been reported.The level of HoxA1, A2 and A10 mRNA expression was decreased by phenylacetate in glioma C6 cells.ConclusionsHoxA1, A2, A4, A6, A7, A9 and A10 genes implicated expression may be involved in glioma organ.HOXA4, A10 genes maybe two new candiation genes in Glioma occur.Phenylacetate can decrease the expression of HoxA1, A2 and A10 in glioma cells, suggesting that PA may act on the transcription process in glioma. |
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