Lamharzi N, Halmos G, Jungwirth A, Schally A V
Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center and Department of Experimental Medicine, Tulane University School of Medicine, New Orleans, LA 70146, USA.
Int J Oncol. 1998 Sep;13(3):429-35. doi: 10.3892/ijo.13.3.429.
Using radioligand binding, RT-PCR, and Southern blot analyses, we evaluated whether agonist [D-Trp6]LH-RH and antagonist Cetrorelix could affect the levels of receptors for LH-RH and EGF and expression of mRNA for these receptors in DU-145 human androgen-independent prostate cancers xenografted into nude mice. Radioligand binding studies showed the presence of specific high affinity receptors for LH-RH and EGF in DU-145 prostate tumors. Cetrorelix, but not [D-Trp6]LH-RH significantly inhibited tumor growth. The concentration of LH-RH receptors was reduced by 22% (p<0. 05) and 67% (p<0.01) after 4 weeks of treatment with [D-Trp6]LH-RH and Cetrorelix respectively. The concentration of EGF receptors fell by 48% (p<0.05) in the [D-Trp6]LH-RH group, whereas Cetrorelix led to a 66% reduction (p<0.01). The expression of LH-RH and EGF receptor mRNA was investigated by RT-PCR analysis followed by Southern blotting. Densitometric analysis of the developed bands showed that the antagonist Cetrorelix decreased the expression of LH-RH receptor mRNA by 55% (p<0.01) compared to control group while the 20% reduction after treatment with the LH-RH agonist was non-significant. Treatment with [D-Trp6]LH-RH and Cetrorelix also reduced the expression of EGF receptor mRNA by 35% and 68% respectively (both, p<0.01) compared to control group. In conclusion, these data demonstrate that growth inhibition of DU-145 prostate tumors induced by prolonged administration of LH-RH antagonist Cetrorelix is accompanied by a marked decrease in the concentration of LH-RH and EGF receptors as well as in their mRNA levels.
我们运用放射性配体结合、逆转录-聚合酶链反应（RT-PCR）以及Southern印迹分析，评估了激动剂[D-色氨酸6]促黄体生成素释放激素（LH-RH）和拮抗剂西曲瑞克是否会影响移植到裸鼠体内的人雄激素非依赖性前列腺癌DU-145中LH-RH受体和表皮生长因子（EGF）受体的水平以及这些受体的mRNA表达。放射性配体结合研究显示，DU-145前列腺肿瘤中存在LH-RH和EGF的特异性高亲和力受体。西曲瑞克能显著抑制肿瘤生长，但[D-色氨酸6]LH-RH无此作用。分别用[D-色氨酸6]LH-RH和西曲瑞克治疗4周后，LH-RH受体浓度分别降低了22%（p<0.05）和67%（p<0.01）。[D-色氨酸6]LH-RH组中EGF受体浓度下降了48%（p<0.05），而西曲瑞克导致其下降了66%（p<0.01）。通过RT-PCR分析及Southern印迹法研究LH-RH和EGF受体mRNA的表达。对显影条带的光密度分析表明，与对照组相比，拮抗剂西曲瑞克使LH-RH受体mRNA的表达降低了55%（p<0.01），而LH-RH激动剂治疗后降低20%无显著意义。与对照组相比，用[D-色氨酸6]LH-RH和西曲瑞克治疗也分别使EGF受体mRNA的表达降低了35%和68%（均为p<0.01）。总之，这些数据表明，长期给予LH-RH拮抗剂西曲瑞克诱导的DU-145前列腺肿瘤生长抑制伴随着LH-RH和EGF受体浓度及其mRNA水平的显著降低。
