蛋白激酶与细胞分化—两种分化诱导剂对酪氨酸蛋白激酶的抑制

在报道视黄酸(RA)是人肝癌细胞株SMMC-7721分化诱导剂的基础上,本文继续报道8-溴-环磷酸腺苷对该细胞也有分化诱导作用,两者都抑制细胞的增殖,降低γ-谷氨酰转肽酶(γ-GT)比活力和升高(ALP)碱性磷酸酶的比活力。在10μmol/LRA和0.5mmol/L-8-Br-cAMP处理细胞1、3、5天后,胞液和膜性组分中的酪氨酸蛋白激酶(TPK)的比活力均降低,其中RA对胞液TPK的作用在早期较明显,约降低30％,而对膜性TPK的影响则随培养天数而逐渐增加,至第5天下降达50％以上。8Br-cAMP则相反,对胞浆TPK的抑制主要发生在3天以后;约抑制43—53％,而对膜性组分则抑制率逐日降低,在第一天较为明显。因TPK是一个细胞增殖恶变的标志,故RA和8-溴-cAMP对TPK的抑制进一步证明这两种分化诱导剂对SMMC-7721细胞的逆转作用。

Protein Kinase and Cell Differentiation Inhibition of Tyrosine Protein Kinase by Two Inducers of Differentiaation

We have reported that retinoic acid (RA) is a differentiation inducer of human hepatocellular carcinoma cell line SMMC-7721. In the present studies, 8-Bromo cyclic AMP (8-Br-cAMP) also showed the effect of inducing differentiation on this cell line. These two inducers inhibited the cell proliferation of SMMC-7721, decreased the specific activity of γ-glutamyl transferase and increased the specific activity of alkaline phosphatase. After the treatment of 10μmol/L RA or 0.5mmol/L 8-Br-cAMP for 1,3 or 5 days, both the specific activities of tyrosine protein kinase (TPK) in cytosolic and membranous fraction were decreased. The effect of RA on cytosolic TPK was more obvious at the early stage after adding to the culture, the inhibition was about 30％, but the effect on membranous TPK became higher with the longer duration in culture. On the 5th day,the inhibition reached to higher than 50％. In contrast, the inhibition of 8-Br-cAMP on cytosolic TPK was only showed 3 days after adding to the culture, the inhibition was about 43—53％, and the inhibition rate on membranous TPK was only obvious on the first day but decreased day by day during prolonged incubation. TPK is an index of cell proliferation and oncogenesis, therefore the inhibition of RA and 8-Br-cAMP on TPK is a further evidence of the reversion effect on SMMC-7721 cell line of the two differentiation inducers.