Candal F J, Bosse D C, Vogler W R, Ades E W
Biological Products Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333.
Cancer Chemother Pharmacol. 1994;34(2):175-8. doi: 10.1007/BF00685937.
Alkyl-lysophospholipids are a group of anti-cancer compounds that have previously been shown to have the unique feature of being selectively toxic to neoplastic tissues. One of these compounds, ET-18-OCH3, has been used for purging bone marrow of cancer cells in phase I clinical trials. Tumor-induced angiogenesis has been directly correlated with tumor growth and metastasis. In this study, we examined the effect ET-18-OCH3 has on a human microvascular endothelial cell line (HMEC-1), including the following functions: angiogenesis, cell-adhesion molecule expression, and cell-junction integrity. We found that ET-18-OCH3 (in vitro) reversibly inhibited induced angiogenesis at levels that did not affect viability. At lower concentrations, ET-18-OCH3 down-regulated the expression of cell-adhesion molecules and affected the integrity of cell-to-cell junctions. This observation demonstrates this versatile family of compounds to have additional targets of action.
烷基溶血磷脂是一类抗癌化合物,此前已证明它们具有对肿瘤组织有选择性毒性的独特特性。其中一种化合物ET-18-OCH3已用于I期临床试验中清除骨髓中的癌细胞。肿瘤诱导的血管生成与肿瘤生长和转移直接相关。在本研究中,我们研究了ET-18-OCH3对人微血管内皮细胞系(HMEC-1)的影响,包括以下功能:血管生成、细胞粘附分子表达和细胞连接完整性。我们发现ET-18-OCH3(体外)在不影响活力的水平上可逆地抑制诱导的血管生成。在较低浓度下,ET-18-OCH3下调细胞粘附分子的表达并影响细胞间连接的完整性。这一观察结果表明这类多功能化合物还有其他作用靶点。