Adwan Hassan, Bäuerle Tobias, Najajreh Yousef, Elazer Victoria, Golomb Gershon, Berger Martin R
Unit of Toxicology and Chemotherapy, Deutsches Krebsforschungszentrum Heidelberg, D-69120 Heidelberg, Germany.
Int J Oncol. 2004 May;24(5):1235-44.
MDA-MB-231 human breast cancer cells transfected with GFP were used as model to determine the reduction in proliferation, colony formation, and migration in response to agents with anti-metastatic properties. These agents consisted of antisense oligonucleotides (ASOs) directed against osteopontin (OPN), bone sialoprotein II (BSP II), and osteonectin (ON), as well as an antibody directed against BSP II. A bisphosphonate derivative (ibandronate) and an alkylphosphocholine (erucylphospho-NNN-trimethylpropanolamine; ErPC3) were used as positive controls. The ASOs directed against OPN, BSP II and ON suppressed the expression of their respective target proteins by 81%, 74% and 69%, respectively. They were barely but significantly active in inhibiting the proliferation, but intermediately to highly active in inhibiting the colony formation and migration of GFP-MDA-MB-231 breast cancer cells. The antibody against human BSP II was significantly more active than all ASOs used and was equally active or even surpassed the activity of ibandronate and ErPC3 in all three assays. The results obtained suggest a specific anti-metastatic activity of this antibody as well as of the ASOs found effective in decreasing OPN and BSP II expression.
用绿色荧光蛋白（GFP）转染的MDA-MB-231人乳腺癌细胞作为模型，以确定具有抗转移特性的药物对细胞增殖、集落形成和迁移的抑制作用。这些药物包括针对骨桥蛋白（OPN）、骨唾液蛋白II（BSP II）和骨连接蛋白（ON）的反义寡核苷酸（ASO），以及一种针对BSP II的抗体。一种双膦酸盐衍生物（伊班膦酸盐）和一种烷基磷胆碱（芥酰磷-NNN-三甲基丙醇胺；ErPC3）用作阳性对照。针对OPN、BSP II和ON的ASO分别将其各自靶蛋白的表达抑制了81%、74%和69%。它们在抑制增殖方面活性较弱但具有显著性，而在抑制GFP-MDA-MB-231乳腺癌细胞的集落形成和迁移方面则具有中等至高度活性。抗人BSP II抗体的活性明显高于所有使用的ASO，并且在所有三项试验中，其活性与伊班膦酸盐和ErPC3相当，甚至超过了它们。所得结果表明该抗体以及在降低OPN和BSP II表达方面有效的ASO具有特定的抗转移活性。
