Mauceri Helena J, Seetharam Saraswathy, Beckett Michael A, Schumm L Philip, Koons Ann, Gupta Vinay K, Park James O, Manan Abdullah, Lee John Y, Montag Anthony G, Kufe Donald W, Weichselbaum Ralph R
Department of Radiation and Cellular Oncology, Duchossois Center for Advanced Medicine, 5758 S. Maryland Avenue, MC 9006, Chicago, IL 60637, USA.
Cancer Chemother Pharmacol. 2002 Nov;50(5):412-8. doi: 10.1007/s00280-002-0514-7. Epub 2002 Sep 18.
We examined the interaction between cyclophosphamide (CPA) and angiostatin (AS) on the growth of primary Lewis lung carcinoma (LLC) tumors and on the development of LLC pulmonary metastases. We studied the effects of AS and CPA on the stages of angiogenesis employing in vitro assays.
Primary tumor growth and pulmonary metastases were measured to evaluate the effects of treatment with AS alone, CPA alone or the combination of CPA and AS. We examined the effects of CPA plus AS on endothelial cell (HUVEC) survival, migration and tube formation.
Combined treatment with CPA and AS did not significantly affect primary tumor growth when compared with CPA treatment alone. However, a significant decrease in the number of pulmonary metastases was observed following CPA plus AS treatment when compared with CPA treatment alone ( P<0.001). AS did not enhance CPA-mediated HUVEC cytotoxicity, and CPA failed to enhance AS-mediated inhibition of migration. However, tube formation was inhibited following combined treatment with CPA and AS when compared with either treatment alone.
AS enhanced the antimetastatic effects of CPA without significantly influencing the effects of CPA on primary tumor growth. CPA plus AS inhibited tube formation, suggesting that interrupting specific steps in the angiogenesis process might be an effective approach to the treatment of subclinical distant metastases.
我们研究了环磷酰胺（CPA）与血管抑素（AS）对原发性Lewis肺癌（LLC）肿瘤生长及LLC肺转移发生的相互作用。我们采用体外试验研究了AS和CPA对血管生成各阶段的影响。
通过测量原发性肿瘤生长及肺转移情况来评估单独使用AS、单独使用CPA或CPA与AS联合使用的治疗效果。我们检测了CPA加AS对内皮细胞（HUVEC）存活、迁移及管腔形成的影响。
与单独使用CPA治疗相比，CPA与AS联合治疗对原发性肿瘤生长无显著影响。然而，与单独使用CPA治疗相比，CPA加AS治疗后肺转移数量显著减少（P<0.001）。AS未增强CPA介导的HUVEC细胞毒性，且CPA未能增强AS介导的迁移抑制作用。然而，与单独使用任一治疗相比，CPA与AS联合治疗后管腔形成受到抑制。
AS增强了CPA的抗转移作用，而对CPA对原发性肿瘤生长的影响无显著影响。CPA加AS抑制管腔形成，提示阻断血管生成过程中的特定步骤可能是治疗亚临床远处转移的有效方法。
