一种外源性细胞周期蛋白依赖性激酶（CDK）抑制剂丁内酯-I，可在p53基因发生突变的胰腺癌细胞中通过提高Bax/Bcl-2比值来诱导细胞凋亡。

An exogenous cdk inhibitor, butyrolactone-I, induces apoptosis with increased Bax/Bcl-2 ratio in p53-mutated pancreatic cancer cells.

作者信息

Wada M, Hosotani R, Lee J U, Doi R, Koshiba T, Fujimoto K, Miyamoto Y, Tsuji S, Nakajima S, Okuyama A, Imamura M

机构信息

Department of Surgery and Surgical Basic Science, Kyoto University, Japan.

出版信息

Anticancer Res. 1998 Jul-Aug;18(4A):2559-66.

PMID:9703910

Abstract

We investigated the effects of an exogenous cdk inhibitor, butyrolactone-I, on cell growth inhibition, apoptosis induction, and the regulation of apoptosis in pancreatic cancer cells with mutated p53. Cell growth was dose-dependently inhibited by Butyrolactone-I in PANC-1 and AsPC-1 cells. Phosphorylation of pRb and Cyclin A expression were significantly inhibited in Butyrolactone-I-treated cells. Apoptotic cell death was detected by both Hoechst staining and TUNEL assay. In butyrolactone-I-treated PANC-1 cells, expression of p53 protein was unchanged, but Bax expression was slightly upregulated and Bcl-2 expression was predominantly down-regulated. Bax/Bcl-2 ratio reached 9.6-fold increase compared to the control at the maximum. The time course of changes in Bax/Bcl-2 ratio was similar to that in the TUNEL-positive ratio. These data, suggest that dynamic changes of the Bax/Bcl-2 ratio might be important in determining point of apoptosis induction in pancreatic cancer cells with p53 mutation.

摘要

我们研究了外源性细胞周期蛋白依赖性激酶（cdk）抑制剂丁内酯-I对p53基因发生突变的胰腺癌细胞的细胞生长抑制、凋亡诱导及凋亡调控的影响。丁内酯-I对PANC-1和AsPC-1细胞的细胞生长具有剂量依赖性抑制作用。在丁内酯-I处理的细胞中，pRb的磷酸化及细胞周期蛋白A的表达均受到显著抑制。通过Hoechst染色和TUNEL检测均发现了凋亡性细胞死亡。在丁内酯-I处理的PANC-1细胞中，p53蛋白的表达未发生变化，但Bax表达略有上调，而Bcl-2表达则主要下调。Bax/Bcl-2比值最高时相比对照组增加了9.6倍。Bax/Bcl-2比值的变化时间进程与TUNEL阳性率的变化时间进程相似。这些数据表明，Bax/Bcl-2比值的动态变化可能在决定p53突变的胰腺癌细胞凋亡诱导点方面具有重要作用。