Tahmatzopoulos A, Gudegast C, Stöckle M, Wullich B, Unteregger G, Zwergel U, Zwergel T
Klinik für Urologie und Kinderurologie, Universitätskliniken des Saarlandes, Homburg/Saar, Germany.
Aktuelle Urol. 2004 Nov;35(6):491-6. doi: 10.1055/s-2004-830048.
New perspectives in prostate cancer genesis and putative clinical management have emerged in recent years . Apoptosis plays a major role in this environment. Proteasome inhibitors block the action of a multicatalytic proteinase complex involved in the degradation of intracellular proteins, particularly with regard to cell cycle regulation and apoptosis. Numerous in vitro studies have demonstrated the ability of these compounds to induce apoptosis and enhance the activity of conventional tumoricidal agents in many cancer cell types, including prostate cancer cells. They point out the use of these potent inhibitors as a new potential molecular approach to the therapeutic management of prostate cancer. Furthermore, the action of proteasome inhibitors has been tested in animal models and in patients with hormone refractory prostate cancer, resulting in both PSA and tumor volume decrease. PS-341 (bortezomib, Velcade) is the first proteasome inhibitor with clinical application in cancer therapy that has been used in clinical trials to date. This report reviews the current status of those papers that have tried to analyze the connection between the proteasome pathway and apoptosis. We present our results of proteasome inhibition in individual prostate cancer cell lines. Proteasomal inhibition may offer a new therapeutic access in "molecular targeting" of prostate cancer.
近年来，前列腺癌发生机制及假定的临床管理方面出现了新的观点。细胞凋亡在这种情况下起着重要作用。蛋白酶体抑制剂可阻断参与细胞内蛋白质降解的多催化蛋白酶复合物的作用，尤其是在细胞周期调控和细胞凋亡方面。大量体外研究表明，这些化合物能够在包括前列腺癌细胞在内的多种癌细胞类型中诱导细胞凋亡并增强传统杀瘤剂的活性。它们指出将这些强效抑制剂用作前列腺癌治疗管理的一种新的潜在分子方法。此外，蛋白酶体抑制剂的作用已在动物模型和激素难治性前列腺癌患者中进行了测试，结果导致前列腺特异性抗原（PSA）水平和肿瘤体积下降。PS-341（硼替佐米，万珂）是首个在癌症治疗中具有临床应用价值的蛋白酶体抑制剂，迄今为止已用于临床试验。本报告回顾了那些试图分析蛋白酶体途径与细胞凋亡之间联系的论文的现状。我们展示了在单个前列腺癌细胞系中蛋白酶体抑制的结果。蛋白酶体抑制可能为前列腺癌的“分子靶向”提供一种新的治疗途径。
