Roomi M Waheed, Ivanov Vadim, Kalinovsky Tatiana, Niedzwiecki Aleksandra, Rath Matthias
Matthias Rath Research Institute, Cancer Division, Santa Clara, CA 95050, USA.
Oncol Rep. 2006 Nov;16(5):943-7.
Five-year survival is limited to 60% in renal cancer patients at diagnosis. Due to the cancer's resistance to conventional treatments and associated high morbidity, we investigated the antimetastatic effects of a specific nutrient mixture (NM) containing lysine, proline, arginine, ascorbic acid and green tea extract on human renal adenocarcinoma cell line 786-0 by measuring: cell proliferation, modulation of MMP-2 and -9 secretion, and cancer cell invasive potential. Human renal cancer cell line 786-0 (ATCC) was grown in RPMI medium in 24-well tissue culture plates. At near confluence, the cells were treated with NM, dissolved in media, and tested at 0, 10, 50, 100, 500 and 1000 microg/ml in triplicate at each dose. Cells were also treated with PMA 200 ng/ml to study enhanced MMP-9 activity. Cell proliferation was evaluated by MTT assay, MMP secretion by gelatinase zymography, and invasion through Matrigel. Zymography demonstrated MMP-2 and MMP-9 secretion by uninduced renal cancer cells with enhanced MMP-9 induced by PMA (200 ng/ml) treatment. NM inhibited the secretion of both MMPs in a dose-dependent fashion with virtual total inhibition of MMP-2 at 500-microg/ml concentration and MMP-9 at 100 microg/ml. The invasion of renal cancer cells through Matrigel was totally inhibited (p=0.0001) by NM at 1000 microg/ml concentration. Our results support a potential role for the nutrient mixture tested in the treatment of renal cell carcinoma, by inhibition of MMP-2 and MMP-9 secretion and invasion.
肾癌患者确诊时的五年生存率仅为60%。由于该癌症对传统治疗具有抗性且相关发病率高,我们通过测量细胞增殖、MMP - 2和 - 9分泌的调节以及癌细胞侵袭潜力,研究了一种含有赖氨酸、脯氨酸、精氨酸、抗坏血酸和绿茶提取物的特定营养混合物(NM)对人肾腺癌细胞系786 - 0的抗转移作用。人肾癌细胞系786 - 0(ATCC)在24孔组织培养板中的RPMI培养基中培养。接近汇合时,用溶解于培养基中的NM处理细胞,并在0、10、50、100、500和1000微克/毫升的浓度下进行一式三份测试。细胞还用200纳克/毫升的佛波酯(PMA)处理以研究增强的MMP - 9活性。通过MTT法评估细胞增殖,通过明胶酶谱法评估MMP分泌,并通过基质胶评估侵袭。酶谱分析显示未诱导的肾癌细胞分泌MMP - 2和MMP - 9,PMA(200纳克/毫升)处理可增强MMP - 9分泌。NM以剂量依赖性方式抑制两种MMP的分泌,在500微克/毫升浓度下几乎完全抑制MMP - 2,在100微克/毫升浓度下几乎完全抑制MMP - 9。在1000微克/毫升浓度下,NM完全抑制(p = 0.0001)肾癌细胞通过基质胶的侵袭。我们的结果支持了所测试的营养混合物通过抑制MMP - 2和MMP - 9分泌及侵袭在肾细胞癌治疗中的潜在作用。