Lang M E, Lottersberger C, Roth B, Böck G, Recheis H, Sgonc R, Stürzl M, Albini A, Tschachler E, Zangerle R, Donini S, Feichtinger H, Schwarz S
Institute of General & Experimental Pathology, University of Innsbruck, Austria.
AIDS. 1997 Sep;11(11):1333-40.
Elucidation of the mechanisms of the previously shown growth-inhibitory action of human chorionic gonadotropin (hCG) on Kaposi's sarcoma (KS) cells and the role of the luteinizing hormone/hCG receptor (hCGR).
Analysis of KS tissues and cultured spindle-type KS cells for the presence of the hCGR using 125I-hCG binding and reverse transcriptase-polymerase chain reaction; analysis of several hCG preparations (urinary, recombinant, isolated alpha and beta subunits); analysis of apoptosis mechanisms by several assays including using z-Val-Ala-Asp-fluoromethylketone (zVAD-FMK), a known apoptosis-inhibitory drug.
First, we found that some urinary preparations of hCG (e.g., CG-10, Steris Profasi) were indeed KS-killing but others (such as Pregnyl, Choragon, Serono Profasi) were not. Secondly, recombinant subunits (alpha as well as beta) of hCG were KS cell-killing but recombinant intact hCG was not. Thirdly, the hCGR message and protein were undetectable in KS. Fourthly, CG10-induced cell death occurred by apoptosis and KS cells could be rescued by preincubation with zVAD-FMK. Finally, we also found that normal peripheral blood lymphocytes (PBL) were killed by CG-10.
It is proposed that the action of subunits or subunit fragments of hCG, mediated by a putative orphan receptor (as opposed to the hCGR) and executed by interleukin-1-converting enzyme (ICE)-like protease(s), constitutes a novel apoptosis mechanism effective towards KS cells, but PBLs and possibly other cells as well. These results provide a basis for testing in vitro the therapeutic efficacy of hCG preparations which, in turn, should improve current clinical trials with 'hCG' in patients who have KS.
阐明先前显示的人绒毛膜促性腺激素（hCG）对卡波西肉瘤（KS）细胞的生长抑制作用机制以及促黄体生成素/hCG受体（hCGR）的作用。
使用¹²⁵I-hCG结合和逆转录聚合酶链反应分析KS组织和培养的纺锤型KS细胞中hCGR的存在情况；分析几种hCG制剂（尿源性、重组型、分离的α和β亚基）；通过多种检测方法分析凋亡机制，包括使用已知的凋亡抑制药物z-缬氨酸-丙氨酸-天冬氨酸-氟甲基酮（zVAD-FMK）。
首先，我们发现一些尿源性hCG制剂（如CG-10、Steris Profasi）确实能杀死KS细胞，但其他制剂（如Pregnyl、Choragon、Serono Profasi）则不能。其次，hCG的重组亚基（α和β）能杀死KS细胞，但重组完整hCG则不能。第三，在KS中未检测到hCGR的信使核糖核酸和蛋白质。第四，CG10诱导的细胞死亡通过凋亡发生，并且KS细胞可以通过与zVAD-FMK预孵育而被挽救。最后，我们还发现正常外周血淋巴细胞（PBL）被CG-10杀死。
有人提出，hCG亚基或亚基片段的作用由一种假定的孤儿受体介导（与hCGR相对），并由白细胞介素-1转化酶（ICE）样蛋白酶执行，构成一种对KS细胞有效的新型凋亡机制，对PBL以及可能的其他细胞也有效。这些结果为体外测试hCG制剂的治疗效果提供了基础，进而应改善目前对患有KS的患者进行的“hCG”临床试验。
