Ahn S G, Jeong S Y, Rhim H, Kim I K
Department of Biochemistry, College of Medicine, The Catholic University of Korea, 505, Banpo-Dong, Socho-Ku, Seoul 137-701, South Korea.
Biochim Biophys Acta. 1998 Nov 19;1448(1):115-25. doi: 10.1016/s0167-4889(98)00113-x.
Prostaglandin (PG) A2 (PGA2) and Delta12-PGJ2 have potent antiproliferative activity on various tumor cell growths in vitro. In this study, we investigated the mechanism of PGA2/Delta12-PGJ2-mediated apoptosis, including intracellular apoptosis-related genes in human hepatocarcinoma Hep3B cells. Hep3B cells treated with PGA2/Delta12-PGJ2 showed that a time-dependent DNA fragmentation characterized by marked apoptosis and the elevation of c-myc mRNA expression. In proportion to the increased c-myc gene transcription, heat shock protein 70 (hsp70) mRNA was induced from 1 to 24 h after PGA2/Delta12-PGJ2 treatment. The transfection of c-myc antisense oligomers in Hep3B cells significantly delayed the induction of HSP70 expression and blocked formation of DNA fragmentation by PGA2/Delta12-PGJ2. Moreover, overexpressed HSP70 showed an increased resistance to apoptosis by PGA2/Delta12-PGJ2 treatment. These results demonstrated that the decreased survival in response to PGA2/Delta12-PGJ2 was causally related to the amount of c-myc and the induction of c-myc regulated the elevation of HSP70 which have been known to correlate with a resistance to apoptosis.
前列腺素（PG）A2（PGA2）和Δ12 - PGJ2在体外对多种肿瘤细胞生长具有强大的抗增殖活性。在本研究中，我们研究了PGA2/Δ12 - PGJ2介导的细胞凋亡机制，包括人肝癌Hep3B细胞中与细胞内凋亡相关的基因。用PGA2/Δ12 - PGJ2处理的Hep3B细胞显示出以明显凋亡和c - myc mRNA表达升高为特征的时间依赖性DNA片段化。与c - myc基因转录增加成比例，在PGA2/Δ12 - PGJ2处理后1至24小时诱导热休克蛋白70（hsp70）mRNA。在Hep3B细胞中转染c - myc反义寡聚物显著延迟了HSP70表达的诱导，并阻断了PGA2/Δ12 - PGJ2诱导的DNA片段化形成。此外，过表达的HSP70显示出对PGA2/Δ12 - PGJ2处理诱导的细胞凋亡的抗性增加。这些结果表明，对PGA2/Δ12 - PGJ2反应中存活率的降低与c - myc的量因果相关，并且c - myc的诱导调节了HSP70的升高，已知HSP70与细胞凋亡抗性相关。
