Cook J R, Schwartz C E, Fausel E D, Chiu J F
Cancer Res. 1985 Jul;45(7):3215-9.
Sodium butyrate has been reported to induce cellular differentiation and reduce the tumorigenicity of certain tumor cells. We have examined the effects of butyrate on alpha-fetoprotein (AFP) gene expression in 7777 and McA-RH8994 rat hepatoma cells and have found that nontoxic concentrations of the drug decrease AFP mRNA levels in both cell lines. However, McA-RH8994 requires a 10-fold lower concentration (0.5 mM) of butyrate to affect a 50% reduction in AFP mRNA levels within 48 h. At 2 mM, sodium butyrate reduces AFP mRNA levels in McA-RH8994 cells by at least 90% after 48 h, while having little effect on the expression of either the 7S RNA or Harvey-ras genes. Time-course studies show that the effect of butyrate on McA-RH8994 AFP mRNA levels is immediate and is accompanied by an accumulation of cells in the G1/G0 phase of the cell cycle. Sodium butyrate was found to reduce AFP mRNA levels in both dexamethasone-treated 7777 and McA-RH8994 cells; dexamethasone decreases AFP mRNA levels in the former cell line and increases AFP mRNA levels in the latter. Therefore, it is unlikely that butyrate acts simply by reducing the dexamethasone receptor concentration in 7777 cells.
据报道，丁酸钠可诱导细胞分化并降低某些肿瘤细胞的致瘤性。我们研究了丁酸盐对7777和McA - RH8994大鼠肝癌细胞中甲胎蛋白（AFP）基因表达的影响，发现该药物的无毒浓度可降低两种细胞系中的AFP mRNA水平。然而，McA - RH8994细胞需要低10倍浓度（0.5 mM）的丁酸盐才能在48小时内使AFP mRNA水平降低50%。在2 mM浓度下，48小时后丁酸钠可使McA - RH8994细胞中的AFP mRNA水平降低至少90%，而对7S RNA或哈维 - ras基因的表达几乎没有影响。时间进程研究表明，丁酸盐对McA - RH8994细胞AFP mRNA水平的影响是即时的，并且伴随着细胞在细胞周期的G1/G0期的积累。发现丁酸钠可降低地塞米松处理的7777和McA - RH8994细胞中的AFP mRNA水平；地塞米松可降低前一种细胞系中的AFP mRNA水平，并增加后一种细胞系中的AFP mRNA水平。因此，丁酸盐不太可能仅仅通过降低7777细胞中的地塞米松受体浓度起作用。
