Motomura S
Department of Obstetrics and Gynecology, Kurume University School of Medicine, Japan.
Kurume Med J. 1998;45(1):27-32. doi: 10.2739/kurumemedj.45.27.
Gonadotropin releasing hormone (GnRH) agonist suppresses the growth of the cancer cells in vitro. To evaluate the effect of a GnRH agonist (GnRHA) in ovarian carcinomas, we investigated the interactions of GnRHA with the KOC-2s human ovarian cancer cells. The addition of GnRHA (10(-8)-10(-6)M) produced an increase 20-30% in the number of cells (p < 0.05). GnRHA (10(-5) M) produced a slight, statistically insignificant decrease of < 10% in the cell count. No DNA fragmentation was produced by GnRHA (10(-8)-10(-6)M). However, GnRHA (10(-5)M) produced internucleosomal cleavage of DNA into fragments with multiples of 180 to 200 bp. This DNA "ladder" pattern is characteristic of apoptosis. The amount of Fas antigen was reduced by each concentration of GnRHa. The addition of GnRHA (10(-6)M and 10(-5)M) significantly increased the secretion of TNF-alpha (p < 0.001). The time- and dose-dependent effects of GnRHA might be confined to the KOC-2s cells as demonstrated by growth inhibitions and characteristic internucleosomal DNA fragmentation. However, the effects of GnRHA on secretion of TNF-alpha and the expression of Fas antigen differed. The present results provide a basis for future studies on the mechanism of apoptotic effect of GnRHA.
促性腺激素释放激素（GnRH）激动剂在体外可抑制癌细胞生长。为评估GnRH激动剂（GnRHA）对卵巢癌的作用，我们研究了GnRHA与KOC-2s人卵巢癌细胞的相互作用。添加GnRHA（10^(-8)-10^(-6)M）可使细胞数量增加20%-30%（p<0.05）。GnRHA（10^(-5)M）使细胞计数略有下降，降幅<10%，但无统计学意义。GnRHA（10^(-8)-10^(-6)M）未引起DNA片段化。然而，GnRHA（10^(-5)M）可使DNA发生核小体间切割，形成180至200bp倍数的片段。这种DNA“梯形”模式是细胞凋亡的特征。每种浓度的GnRHa均可使Fas抗原量减少。添加GnRHA（10^(-6)M和10^(-5)M）可显著增加TNF-α的分泌（p<0.001）。如生长抑制和特征性核小体间DNA片段化所示，GnRHA的时间和剂量依赖性效应可能仅限于KOC-2s细胞。然而，GnRHA对TNF-α分泌和Fas抗原表达的影响有所不同。本研究结果为进一步研究GnRHA凋亡作用机制提供了依据。
