Opolski A, Mazurkiewicz M, Wietrzyk J, Kleinrok Z, Radzikowski C
Dept. of Tumor Immunology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw.
J Exp Clin Cancer Res. 2000 Sep;19(3):383-90.
In this paper we described the results of our studies on the baclophen (gamma aminobutyric acid (GABA)-B receptor agonist) inhibitory effect on the growth of experimental mammary cancer 16/C in mice and on the estimation of GABA level and GAD (glutamine acid decarboxylase--the key enzyme in GABA synthesis) activity after this treatment in mice. The experimental data are confronted with the estimation of GABA level and GAD activity in human mammary gland material taken from the patients with benign breast tumors of different pathological and age related hormonal stages. A significant inhibition of 16/C tumor growth in treated with baclophen mice was observed. Mean GABA level and GAD activity were significantly higher both in tumor and in normal tissue of baclophen treated mice in comparison to control animals. The results of clinical studies have shown that the lowest GABA level and GAD activity in tumor and normal mammary gland tissue was detected in patients in peri-menopausal stage. Both, in human and mouse material, the GABA level and GAD activity were higher in tumor than in normal tissue and there was a clear positive correlation between GABA level and GAD activity in both tissues studied. GABA level and GAD activity in tumor and in normal tissue were lower in patients with dysplasia than in patients with fibroadenoma. Considering our results, namely an inhibitory effect of GABA receptor agonist on mammary cancer growth and the correlation between GABA level and the stage of breast pathology and/or hormonal activity, it seems probable that GABA-ergic system is involved in hormonal regulation and pathogenesis of breast cancer.
在本文中，我们描述了有关巴氯芬（γ-氨基丁酸（GABA）-B受体激动剂）对小鼠实验性乳腺癌16/C生长的抑制作用以及对经该处理后的小鼠体内GABA水平和谷氨酸脱羧酶（GAD，GABA合成中的关键酶）活性评估的研究结果。将实验数据与取自处于不同病理和年龄相关激素阶段的良性乳腺肿瘤患者的人乳腺组织材料中的GABA水平和GAD活性评估结果进行了对比。观察到用巴氯芬处理的小鼠中16/C肿瘤生长受到显著抑制。与对照动物相比，巴氯芬处理的小鼠的肿瘤和正常组织中的平均GABA水平和GAD活性均显著更高。临床研究结果表明，在围绝经期患者的肿瘤和正常乳腺组织中检测到最低的GABA水平和GAD活性。在人和小鼠材料中，肿瘤中的GABA水平和GAD活性均高于正常组织，并且在研究的两种组织中GABA水平和GAD活性之间存在明显的正相关。发育异常患者的肿瘤和正常组织中的GABA水平和GAD活性低于纤维腺瘤患者。考虑到我们的结果，即GABA受体激动剂对乳腺癌生长的抑制作用以及GABA水平与乳腺病理阶段和/或激素活性之间的相关性，GABA能系统似乎可能参与乳腺癌的激素调节和发病机制。
