Roomi M Waheed, Ivanov Vadim, Kalinovsky Tatiana, Niedzwiecki Aleksandra, Rath Matthias
Matthias Rath Research Institute, Cancer Division, 1260 Memorex Drive, Santa Clara, CA 95050, USA.
Med Oncol. 2006;23(1):105-11. doi: 10.1385/mo:23:1:105.
Current treatment of fibrosarcoma, an aggressive cancer of the connective tissue, is generally associated with poor prognosis. Matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), and constituents of the extracellular matrix (ECM), such as fibronectin, play a critical role in angiogenesis and underlie neoplastic invasion and metastasis. This and anticancer properties of lysine, proline, arginine, ascorbic acid, and green tea extract (NM) prompted us to investigate the effect of these nutrients in vitro on human fibrosarcoma cells HT-1080 by measuring cell proliferation, modulation of MMP-2 and MMP-9, and invasive potential. In vivo, we studied the growth of human fibrosarcoma HT-1080 cells in athymic nude mice and the expression of MMPs and VEGF. Cell proliferation was evaluated by MTT assay, MMP expression by gelatinase zymography, and invasion through Matrigel and migration by scratch assay. Tumors were excised, weighed, and processed for histology in both the control and nutrient-supplemented groups. Results showed NM inhibited the growth and reduced the size of tumors in nude mice; decreased MMP-9 and VEGF secretion was found in the supplemented group tissues. NM inhibited invasion through Matrigel and migration with total inhibition at 1,000 microg/mL. These results offer promise in the therapeutic use of the nutrient mixture of lysine, proline, arginine, ascorbic acid, and green tea extract tested in the treatment of fibrosarcoma.
纤维肉瘤是一种侵袭性的结缔组织癌症，目前的治疗方法通常预后较差。基质金属蛋白酶（MMPs）、血管内皮生长因子（VEGF）以及细胞外基质（ECM）的成分，如纤连蛋白，在血管生成中起关键作用，也是肿瘤侵袭和转移的基础。赖氨酸、脯氨酸、精氨酸、抗坏血酸和绿茶提取物（NM）的这种及抗癌特性促使我们通过测量细胞增殖、MMP - 2和MMP - 9的调节以及侵袭潜力，来研究这些营养素在体外对人纤维肉瘤细胞HT - 1080的影响。在体内，我们研究了人纤维肉瘤HT - 1080细胞在无胸腺裸鼠中的生长情况以及MMPs和VEGF的表达。通过MTT法评估细胞增殖，通过明胶酶谱法评估MMP表达，通过基质胶侵袭实验和划痕实验评估迁移。对对照组和补充营养素组的肿瘤进行切除、称重并进行组织学处理。结果显示，NM抑制了裸鼠肿瘤的生长并减小了肿瘤大小；在补充组组织中发现MMP - 9和VEGF分泌减少。NM抑制了通过基质胶的侵袭和迁移，在1000μg/mL时完全抑制。这些结果为赖氨酸、脯氨酸、精氨酸、抗坏血酸和绿茶提取物的营养混合物在纤维肉瘤治疗中的治疗应用带来了希望。
