Fife R S, Sledge G W
Department of Medicine, Indiana University School of Medicine, Indianapolis 46202.
J Lab Clin Med. 1995 Mar;125(3):407-11.
Metastatic disease is one of the major causes of death from cancer in human beings. Several enzyme systems have been implicated in the metastatic process, but the metalloproteinases (MPs) appear to be the major group involved in most instances of neoplastic invasion. Increased MP activity has been correlated with the metastatic potential of many cancers, including breast cancer. MPs also play a role in tumor angiogenesis. Tetracyclines are antimicrobial agents that can suppress MP activity in a variety of tissues, including gingiva, bone, and cartilage. Several reports have indicated that tetracyclines can suppress tumor MPs as well. A synthetic tetracycline, doxycycline, inhibits migration of human MDA-MB-435 breast adenocarcinoma cells through a reconstituted basement membrane (Matrigel), an assay used as an in vitro surrogate for the in vivo process of tumor invasion through basement membranes. Additionally, doxycycline diminishes the proliferation of this breast cancer cell line and also decreases its gelatinolytic activity, as determined by gel zymography.
转移性疾病是人类癌症死亡的主要原因之一。几种酶系统与转移过程有关，但金属蛋白酶（MPs）似乎是大多数肿瘤侵袭病例中涉及的主要酶类。MP活性增加与许多癌症（包括乳腺癌）的转移潜能相关。MPs在肿瘤血管生成中也起作用。四环素是抗菌剂，可抑制包括牙龈、骨骼和软骨在内的多种组织中的MP活性。几份报告表明，四环素也能抑制肿瘤MPs。一种合成四环素——强力霉素，可抑制人MDA-MB-435乳腺腺癌细胞通过重组基底膜（基质胶）的迁移，基质胶实验是一种用于体外模拟肿瘤通过基底膜进行体内侵袭过程的实验。此外，强力霉素可减少该乳腺癌细胞系的增殖，并通过凝胶酶谱法测定降低其明胶酶活性。
