Roomi M Waheed, Ivanov Vadim, Kalinovsky Tatiana, Niedzwiecki Aleksandra, Rath Matthias
Oncology Division, Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA, 95050, USA.
Med Oncol. 2007;24(2):231-8. doi: 10.1007/BF02698045.
Standard multimodality therapy of gliomas is associated with poor patient survival and significant toxicity. Abnormal expression of matrix metalloproteinases is associated with tumor growth and invasion. Based on reported antitumor properties, we investigated the effect of a combination of natural compounds (NM), primarily composed of lysine, proline, ascorbic acid, and green tea extract in vitro on glioma cell line A-172, by measuring MMP secretion, invasion through Matrigel, and cell proliferation. Glioma cells A-172 (ATCC) were grown in modified Dulbecco's Eagle medium with 10% fetal bovine serum and antibiotics and treated with NM at 0, 10, 50, 100, 500, and 1000 microg/mL concentration in triplicate at each dose. Cell proliferation was assayed by MTT, MMP secretion by zymography, invasion through Matrigel, and morphology by H&E staining. Zymography showed one band corresponding to MMP-2, which was inhibited by NM in a dose-dependent fashion, with virtual total inhibition at 500-microg/mL concentration. Invasion through Matrigel was completely inhibited at 1000 microg/mL NM. NM was not toxic to glioma cell line A-172 at lower concentrations and exhibited toxicity of 50% over the control at 1000 microg/mL. NM significantly inhibited MMP secretion and invasion-important parameters for cancer prevention, suggesting a possible therapeutic role.
胶质瘤的标准多模态治疗与患者生存率低和显著毒性相关。基质金属蛋白酶的异常表达与肿瘤生长和侵袭有关。基于已报道的抗肿瘤特性,我们通过测量基质金属蛋白酶(MMP)分泌、穿过基质胶的侵袭能力和细胞增殖,研究了主要由赖氨酸、脯氨酸、抗坏血酸和绿茶提取物组成的天然化合物组合(NM)在体外对胶质瘤细胞系A-172的影响。胶质瘤细胞A-172(美国典型培养物保藏中心)在含有10%胎牛血清和抗生素的改良杜尔贝科氏伊格尔培养基中培养,并在每个剂量下以0、10、50、100、500和1000μg/mL的浓度一式三份地用NM处理。通过MTT法检测细胞增殖,通过酶谱法检测MMP分泌,通过基质胶侵袭实验检测侵袭能力,通过苏木精和伊红染色检测形态。酶谱显示一条对应于MMP-2的条带,其被NM以剂量依赖性方式抑制,在500μg/mL浓度时几乎完全抑制。在1000μg/mL NM时,穿过基质胶的侵袭完全被抑制。NM在较低浓度下对胶质瘤细胞系A-172无毒,在1000μg/mL时显示出比对照高50%的毒性。NM显著抑制MMP分泌和侵袭,这是癌症预防的重要参数,提示其可能具有治疗作用。