Dr Rath Research Institute, Santa Clara, CA 95050, USA.
Oncol Rep. 2010 Sep;24(3):747-57. doi: 10.3892/or_00000917.
Type IV collagenase matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9, have been found to promote invasion and metastasis of malignant tumors. Extracellular matrix (ECM) degradation by MMPs and increased expression of MMPs in cancer cells and tumor microvascular endothelial cells make MMPs an attractive target for cancer. Focused on a common pathomechanism of cancer growth and invasion, the disintegration of connective tissue, we used natural approaches to increase the integrity and strength of connective tissues. Utilizing the principle of nutrition synergy, we developed a novel micronutrient mixture (NM) containing lysine, proline, ascorbic acid and green tea extract. This study evaluates the potency of the components EGCG and green tea extract independently compared to that of NM on modulation of patterns of MMP-2 and MMP-9 expression in four cancer cell lines expressing MMP-2, MMP-9 or both. Human fibrosarcoma (HT-1080), hepatocellular carcinoma (SK-Hep-1), glioblastoma (T-98G), uterine leiomyosarcoma (SK-UT-1) cell lines were obtained from ATCC and grown in minimum essential medium (MEM) supplemented with 10% FBS, penicillin (100 U/ml) and streptomycin (100 mg/ml) in 24-well tissue culture plates. At near confluence, the cells were treated with agents dissolved in media and tested at concentrations indicated in triplicate at each dose. Cells were also treated with PMA 100 ng/ml to study enhanced expression of MMP-9. MMP expression was assessed by gelatinase zymography. Fibrosarcoma and hepatocellular carcinoma cells expressed both MMP-2 and MMP-9. Glioblastoma cells expressed MMP-2 and PMA treatment induced MMP-9 expression. Uterine leimyosarcoma cells expressed no MMPs but PMA induced MMP-9. NM was the most potent dose-dependent inhibitor of MMPs, followed by green tea extract and EGCG. In conclusion, these results suggest the enhanced efficacy of nutrients working in synergy to modulate complex pathways such as MMP expression.
IV 型胶原酶基质金属蛋白酶（MMPs），尤其是 MMP-2 和 MMP-9，已被发现可促进恶性肿瘤的侵袭和转移。MMPs 降解细胞外基质（ECM）以及癌细胞和肿瘤微血管内皮细胞中 MMPs 的表达增加，使 MMPs 成为癌症治疗的一个有吸引力的靶点。本研究聚焦于癌症生长和侵袭的共同病理机制——结缔组织的崩解，我们采用天然方法增加结缔组织的完整性和强度。利用营养协同作用的原理，我们开发了一种新型的微量营养素混合物（NM），其中包含赖氨酸、脯氨酸、抗坏血酸和绿茶提取物。本研究评估了 EGCG 和绿茶提取物各自以及 NM 对四种表达 MMP-2、MMP-9 或两者均表达的癌细胞系中 MMP-2 和 MMP-9 表达模式的调节作用。人纤维肉瘤（HT-1080）、肝癌（SK-Hep-1）、神经胶质瘤（T-98G）、子宫平滑肌肉瘤（SK-UT-1）细胞系购自 ATCC，在添加有 10% FBS、青霉素（100 U/ml）和链霉素（100 mg/ml）的最低必需培养基（MEM）中于 24 孔组织培养板中生长。当接近汇合时，用溶解在培养基中的药物处理细胞，并在每个剂量的 3 个重复孔中测试指示浓度的药物。还使用 PMA 100 ng/ml 处理细胞以研究 MMP-9 的增强表达。通过明胶酶谱法评估 MMP 表达。纤维肉瘤和肝癌细胞均表达 MMP-2 和 MMP-9。神经胶质瘤细胞表达 MMP-2，PMA 处理诱导 MMP-9 表达。子宫平滑肌肉瘤细胞不表达 MMPs，但 PMA 诱导 MMP-9 表达。NM 是最有效的剂量依赖性 MMP 抑制剂，其次是绿茶提取物和 EGCG。总之，这些结果表明，协同作用的营养素增强了调节 MMP 表达等复杂途径的功效。
