Bayne C W, Donnelly F, Ross M, Habib F K
Prostate Research Group, University Department of Oncology, Western General Hospital, Edinburgh, Scotland.
Prostate. 1999 Sep 1;40(4):232-41. doi: 10.1002/(sici)1097-0045(19990901)40:4<232::aid-pros4>3.0.co;2-0.
The aim of this study was to determine the effect of the phytotherapeutic agent, Permixon, on a novel coculture model of benign prostatic hyperplasia (BPH) in an effort to better understand the mode of action of the drug in vivo.
The effect of Permixon, at the calculated therapeutic concentration, on the activity of 5alpha-reductase isoenzymes was evaluated utilizing a pH-specific assay. Prostate-specific antigen (PSA) secretions into the medium were measured in the presence and absence of Permixon and quantified by an ELISA assay. The morphological patterns before and following Permixon treatment were also examined by electron microscopy. All results were compared to controls.
Permixon at a concentration of 10 micrograms/ml (calculated plasma concentration in patient receiving recommended therapeutic dosage) was shown to be an effective inhibitor of both 5alpha-reductase types I and II isoenzymes without influencing the secretion of PSA by the epithelial cells, even after stimulation with testosterone. The morphology of Permixon-treated cells was found to be markedly different from that of untreated controls. Cells which had been treated with the drug demonstrated extensive accumulation of lipids in the cytoplasm and widespread damage of intracellular membranes, including mitochondrial and nuclear membranes.
Permixon is an effective dual inhibitor of 5alpha-reductase isoenzyme activities in the prostate. Unlike other 5alpha-reductase inhibitors, Permixon induces this effect without interfering with the cells' capacity to secrete PSA, thus permitting the continued use of PSA measurements for prostate cancer screening.
本研究的目的是确定植物治疗剂爱普列特（Permixon）对良性前列腺增生（BPH）新型共培养模型的影响，以便更好地了解该药物在体内的作用方式。
利用pH特异性测定法评估爱普列特在计算出的治疗浓度下对5α-还原酶同工酶活性的影响。在有和没有爱普列特的情况下测量培养基中前列腺特异性抗原（PSA）的分泌，并通过酶联免疫吸附测定法进行定量。还通过电子显微镜检查爱普列特处理前后的形态学模式。所有结果均与对照组进行比较。
浓度为10微克/毫升的爱普列特（相当于接受推荐治疗剂量患者的血浆计算浓度）被证明是I型和II型5α-还原酶同工酶的有效抑制剂，即使在用睾酮刺激后也不影响上皮细胞分泌PSA。发现经爱普列特处理的细胞形态与未处理的对照细胞明显不同。用该药物处理的细胞在细胞质中显示出大量脂质积累，并且细胞内膜广泛受损，包括线粒体膜和核膜。
爱普列特是前列腺中5α-还原酶同工酶活性的有效双重抑制剂。与其他5α-还原酶抑制剂不同，爱普列特诱导这种作用而不干扰细胞分泌PSA的能力，从而允许继续使用PSA测量进行前列腺癌筛查。
