Sasaguri T, Masuda J, Shimokado K, Yokota T, Kosaka C, Fujishima M, Ogata J
Research Institute, National Cardiovascular Center, Osaka, Japan.
Exp Cell Res. 1992 Jun;200(2):351-7. doi: 10.1016/0014-4827(92)90182-8.
The effects of prostaglandins (PGs) A and J, which are anti-tumor eicosanoids, on the proliferation of cultured vascular smooth muscle cells were investigated. Serum-stimulated DNA synthesis was potently inhibited by PGA1, PGA2, PGJ2, and delta 12-PGJ2 in similar dose-dependent fashions. The effects of PGA1 and PGA2 were reversible when they were removed from the culture media, whereas recoveries were only partial in the cells treated with PGJ2 and delta 12-PGJ2. PGs were effective even if they were added immediately before entry into S phase. Inhibition of DNA synthesis was sustained when hydroxyurea, which blocks cell cycle at the G1/S border, was added after the removal of PGA2, and vice versa; PGs blocked DNA synthesis when they were added after the removal of hydroxyurea. Levels of c-myc mRNA formed two peaks during the G1 phase, at 1-2 h and at 8-12 h. The PGs did not affect the first elevation, but enhanced the second and sustained it up to 18-24 h, whereas in controls, c-myc mRNA decreased quickly after entry into S phase. The rate of degradation of c-myc mRNA was much smaller in PG-treated cells than in nontreated cells. We conclude, therefore, that PGA and PGJ inhibit a crucial event(s) in the cell cycle occurring at the G1/S border, but that this inhibition is not accompanied by the reduction in c-myc gene expression in contrast with some types of tumor cells treated with PGs.
前列腺素（PGs）A和J属于抗肿瘤类二十烷酸，本研究调查了它们对培养的血管平滑肌细胞增殖的影响。血清刺激的DNA合成受到PGA1、PGA2、PGJ2和δ12 - PGJ2的强烈抑制，且呈相似的剂量依赖性。当从培养基中去除PGA1和PGA2时，其作用是可逆的，而用PGJ2和δ12 - PGJ2处理的细胞仅部分恢复。即使在进入S期前立即添加PGs也有效果。去除PGA2后添加羟基脲（可在G1/S边界阻断细胞周期），DNA合成的抑制作用仍持续存在，反之亦然；去除羟基脲后添加PGs时，PGs会阻断DNA合成。c - myc mRNA水平在G1期形成两个峰值，分别在1 - 2小时和8 - 12小时。PGs不影响第一个峰值升高，但增强第二个峰值并持续至18 - 24小时，而在对照中，进入S期后c - myc mRNA迅速下降。PG处理的细胞中c - myc mRNA的降解速率比未处理的细胞小得多。因此，我们得出结论，PGA和PGJ抑制细胞周期中发生在G1/S边界的关键事件，但与某些用PGs处理的肿瘤细胞类型不同，这种抑制并不伴随着c - myc基因表达的降低。
