Comparative effects of EGCG, green tea and a nutrient mixture on the patterns of MMP-2 and MMP-9 expression in cancer cell lines
Comparative effects of EGCG, green tea and a nutrient mixture on the patterns of MMP-2 and MMP-9 expression in cancer cell lines
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DOI：
10.3892/or_00000917
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发表时间：
2010-09-01
期刊：
影响因子：
4.2
通讯作者：
Niedzwiecki, A.
中科院分区：
文献类型：
--
作者：
Roomi, M. W.;Monterrey, J. C.;Niedzwiecki, A.
IV型胶原酶基质金属蛋白酶（MMP-2和MMP-9）被发现促进恶性肿瘤的侵袭和转移。MMPs降解细胞外基质（ECM）以及MMPs在癌细胞和肿瘤微血管内皮细胞中的表达增加使得MMPs成为有吸引力的癌症靶点。我们专注于癌症生长和侵袭的常见病理机制，即结缔组织的解体，我们使用天然方法来增加结缔组织的完整性和强度。利用营养协同原理，研制了一种新型的含有赖氨酸、脯氨酸、抗坏血酸和绿色茶提取物的微量营养素混合物。本研究评估了组分EGCG和绿色茶提取物与NM相比在表达MMP-2、MMP-9或两者的四种癌细胞系中对MMP-2和MMP-9表达模式的调节的效力。从ATCC获得人纤维肉瘤（HT-1080）、肝细胞癌（SK-Hep-1）、胶质母细胞瘤（T-98 G）、子宫平滑肌肉瘤（SK-UT-1）细胞系，并在24孔组织培养板中在补充有10%FBS、青霉素（100 U/ml）和链霉素（100 mg/ml）的最低必需培养基（MEM）中生长。在接近汇合时，用溶解在培养基中的试剂处理细胞，并在每个剂量下以一式三份的指示浓度进行测试。还用PMA 100 ng/ml处理细胞以研究MMP-9的表达增强。明胶酶谱法检测MMP表达。纤维肉瘤和肝癌细胞表达MMP-2和MMP-9。胶质母细胞瘤细胞表达MMP-2，PMA处理诱导MMP-9表达。子宫平滑肌肉瘤细胞不表达MMP，但PMA诱导MMP-9表达。NM是最有效的MMPs剂量依赖性抑制剂，其次是绿色茶提取物和EGCG。总之，这些结果表明，营养素协同调节MMP表达等复杂途径的功效增强。
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.