去甲二氢愈创木酸对前列腺癌PC-3细胞作用机制的实验研究

目的 观察脂氧合酶抑制剂去甲二氢愈创木酸(NDGA)对前列腺癌PC-3细胞增殖及凋亡的影响并探讨其相关机制. 方法以不同浓度(0、20、40,80和160 μmol/L)的NDGA干预体外培养的前列腺癌PC-3细胞.通过细胞形态学观察、四甲基偶氮唑盐比色法及TUNEL法检测NDGA对PC-3细胞的增殖抑制及诱导凋亡作用,流式细胞术检测其活化Caspase-3的表达情况.结果 40、80、160μmol/L NDGA对PC-3细胞增殖有明显抑制作用,作用强度具有时间和剂量依赖性.0、20、40、80和160μmol/L NIX;A作用48 h后,PC-3细胞凋亡指数分别为(2.9±0.2)%、(3.2±0.3)%、(68.5±0.8)%、(86.2±0.3)%和(86.9±0.6)%,后3组与第1组比较差异有统计学意义(P<0.05).0、20,40、80和160/μmol/L NDGA作用PC-3细胞48 h后活化Caspase-3的阳性率分别为(3.9±0.0)%、(4.1±0.1)%、(55.5±0.8)%、(75.1±0.3)%和(76.3±0.7)%,后3组与第1组比较差异有统计学意义(P<0.05). 结论 NDGA能抑制前列腺癌PC-3细胞增殖、诱导其凋亡,作用呈剂量和时问依赖性,其机制可能与PC-3细胞Caspase-3活化有关.

Experimental study on the mechanism of nordihydroguaiaretic acid on human prostate cancer PC-3 cells

Objective To investigate the effects of nordihydroguaiaretic acid(NDGA), a general lipoxygenase inhibitor, on the proliferation and apoptosis of human prostate cancer PC-3 ceils and ex-plore the mechanism. Methods The cultured PC-3 ceils were exposured to NDGA at the different concentrations of 0 (control group), 20, 40, 80 and 160 μmol/L, respectively. The effect of NDGA on growth inhibition and apoptosis inducement were measured with morphometry, MTT and TUNEL as-say. The activity of caspase-3 was determinated with flow cytometry. Results The survival rate of PC-3 cell decreased significantly after treated with 40, 80, 160 μmol/L NDGA. The apoptosis indices of PC-3 cell dealt with 0, 20, 40, 80 and 160 μmol/L NDGA for 48 h were (2.9±0.2)%, (3.2±0.3)%, (68.5±0.8)%, (86.2±0.3)% and (86.9±0.6)%, respectively. When PC-3 cells were treated with 0, 20, 40, 80, 160 μmol/L NDGA for 48 h, the positive rates of activated caspase-3 were (3.9±0.0)%, (4.15±0.1)%, (55.5±0.8)%, (75.1±0.3)%, and (76.3±0.7)%, respectively. Compared with the control group, the apoptosis indices and positive rates of activated caspase-3 in the groups of 40, 80, and 160 μmol/L NDGA increased significantly(P<0.05). Conclusions NDGA can inhibit the growth and induce apoptosis of PC-3 cells. The mechanism may be related with intra-cellular activation of caspase-3.