Yamamoto T, Tsuda T, Hamamori Y, Nishimura N, Takai Y
Department of Biochemistry, Kobe University School of Medicine, Hyogo.
J Biochem. 1988 Jul;104(1):53-6. doi: 10.1093/oxfordjournals.jbchem.a122422.
Fibroblast growth factor (FGF) plus insulin induced DNA synthesis in and proliferation of NIH/3T3 cells. The protein kinase C-activating phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), inhibited both the DNA synthesis and cell proliferation induced by FGF plus insulin. The concentration of TPA required for 50% inhibition of the DNA synthesis was about 5 nM. Phorbol-12,13-dibutyrate, another protein kinase C-activating phorbol ester, also inhibited the DNA synthesis but 4 alpha-phorbol-12,13-didecanoate, known to be inactive for this enzyme, was ineffective. DNA synthesis started at about 12 h after the addition of FGF plus insulin. The inhibitory action of TPA on the DNA synthesis was observed when it was added within 12 h after the addition of FGF plus insulin. These results suggest that phorbol esters exhibit an antiproliferative action through protein kinase C activation in NIH/3T3 cells, and that this action of phorbol esters is due to inhibition of the progression from the late G1 to the S phase of the cell cycle.
成纤维细胞生长因子（FGF）加胰岛素可诱导NIH/3T3细胞的DNA合成及增殖。蛋白激酶C激活剂佛波酯12-O-十四酰佛波醇-13-乙酸酯（TPA）可抑制FGF加胰岛素诱导的DNA合成及细胞增殖。抑制50%DNA合成所需的TPA浓度约为5 nM。另一种蛋白激酶C激活剂佛波醇-12,13-二丁酸酯也可抑制DNA合成，但已知对该酶无活性的4α-佛波醇-12,13-二癸酸酯则无效。在添加FGF加胰岛素后约12小时开始DNA合成。当在添加FGF加胰岛素后12小时内添加TPA时，可观察到其对DNA合成的抑制作用。这些结果表明，佛波酯通过激活NIH/3T3细胞中的蛋白激酶C发挥抗增殖作用，且佛波酯的这种作用是由于抑制了细胞周期从G1晚期到S期的进程。
