Ueda M, Ueki M, Fujii H, Yoshizawa K, Nakajima M
Department of Obstetrics and Gynecology, Osaka Medical College, Japan.
J Med. 1997;28(3-4):175-90.
The present study was undertaken to investigate the effects of the aminopeptidase inhibitor ubenimex (bestatin) on the invasive activity of cultured human uterine cervical carcinoma cells. The invasion of squamous cell carcinoma OMC-1 and SKG-IIIb cells, and adenocarcinoma OMC-4 and CAC-1 cells into reconstituted basement membrane (Matrigel) was inhibited by the presence of bestatin in a concentration-dependent manner. However, bestatin did not have any effect on tumor cell proliferation or migration. Immunoblot analysis of tumor-conditioned medium showed that the treatment of tumor cells with bestatin resulted in the reduction of the 72 kDa gelatinase level (gelatinase A, latent form) in the four cell lines examined, and the reduction of the 68 kDa gelatinase level (gelatinase A, active form) in SKG-IIIb cells. Bestatin inhibited hydrolyzing activities towards substrates of aminopeptidases in tumor cells, but did not directly inhibit gelatinase A. These results suggest that bestatin may inhibit the invasion of uterine cervical carcinoma cells possibly through the inhibitory mechanisms for production and activation of gelatinase A modulated by tumor aminopeptidases.
本研究旨在探讨氨肽酶抑制剂乌苯美司（抑氨肽酶素）对培养的人子宫颈癌细胞侵袭活性的影响。抑氨肽酶素的存在以浓度依赖的方式抑制了鳞状细胞癌OMC-1和SKG-IIIb细胞以及腺癌OMC-4和CAC-1细胞向重组基底膜（基质胶）的侵袭。然而，抑氨肽酶素对肿瘤细胞的增殖或迁移没有任何影响。对肿瘤条件培养基的免疫印迹分析表明，用抑氨肽酶素处理肿瘤细胞导致在所检测的四种细胞系中72 kDa明胶酶水平（明胶酶A，潜伏形式）降低，在SKG-IIIb细胞中68 kDa明胶酶水平（明胶酶A，活性形式）降低。抑氨肽酶素抑制肿瘤细胞中氨肽酶对底物的水解活性，但不直接抑制明胶酶A。这些结果表明，抑氨肽酶素可能通过对由肿瘤氨肽酶调节的明胶酶A的产生和激活的抑制机制来抑制子宫颈癌细胞的侵袭。
