Ganoderic acid T inhibits tumor invasion in vitro and in vivo through inhibition of MMP expression
Ganoderic acid T inhibits tumor invasion in vitro and in vivo through inhibition of MMP expression
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DOI：
10.1016/s1734-1140(10)70252-8
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发表时间：
2010-01-01
影响因子：
4.4
通讯作者：
Zhong, Jian-Jiang
中科院分区：
文献类型：
--
作者：
Chen, Nian-Hong;Liu, Jian-Wen;Zhong, Jian-Jiang
中国传统的药用蘑菇灵芝在亚洲已经使用了几千年，用于预防和治疗各种疾病，包括癌症。在前期工作中，我们从灵芝中分离纯化了灵芝酸T（GA-T）。lucidum [28].在本研究中，我们调查GA-T的功能，在其体外侵袭和体内转移的影响。台盼蓝染料排斥试验表明GA-T抑制人结肠癌细胞系HCT-116细胞的增殖。细胞聚集和粘附试验表明，GA-T促进同型聚集，同时以剂量依赖性方式抑制HCT-116细胞与细胞外基质（ECM）的粘附。伤口愈合试验表明，GA-T还以剂量依赖性方式抑制HCT-116细胞的迁移，并且以剂量和时间依赖性方式抑制95-D细胞（一种高转移性人肺肿瘤细胞系）的迁移。此外，GA-T抑制核因子-κ B（NF-κ B）的核转位和κ B-α抑制剂（I κ B α）的降解，这导致基质金属蛋白酶-9（MMP-9）、诱导型一氧化氮合酶（iNOS）和尿激酶型纤溶酶原激活剂（uPA）的表达下调。动物和刘易斯肺癌（LLC）模型实验表明，GA-T抑制肿瘤生长和LLC转移，并下调MMP-2和MMP-9 mRNA表达。综上所述，这些结果表明GA-T有效地抑制癌细胞的体外侵袭和体内转移，因此它可能作为一种潜在的治疗癌症的药物。
The traditional Chinese medicinal mushroom, Ganoderma lucidum, has been used in Asia for several thousand years for the prevention and treatment of a variety of diseases, including cancer. In previous work, we purified ganoderic acid T (GA-T) from G. lucidum [28]. In the present study, we investigate the functions of GA-T in terms of its effects on invasion in vitro and metastasis in vivo. A trypan blue dye exclusion assay indicates that GA-T inhibits proliferation of HCT-116 cells, a human colon carcinoma cell line. Cell aggregation and adhesion assays show that GA-T promotes homotypic aggregation and simultaneously inhibits the adhesion of HCT-116 cells to the extracellular matrix (ECM) in a dose-dependent manner. Wound healing assays indicate that GA-T also inhibits the migration of HCT-116 cells in a dose-dependent manner, and it suppresses the migration of 95-D cells, a highly metastatic human lung tumor cell line, in a dose- and time-dependent manner. In addition, GA-T inhibits the nuclear translocation of nuclear factor-kappa B (NF-kappa B) and the degradation of inhibitor of kappa B-alpha (I kappa B alpha), which leads to down-regulated expression of matrix metalloproteinase-9 (MMP-9), inducible nitric oxide synthase (iNOS), and urokinase-type plasminogen activator (uPA). Animal and Lewis Lung Carcinoma (LLC) model experiments demonstrate that GA-T suppresses tumor growth and LLC metastasis and down-regulates MMP-2 and MMP-9 mRNA expression in vivo. Taken together, these results demonstrate that GA-T effectively inhibits cancer cell invasion in vitro and metastasis in vivo, and thus it may act as a potential drug for treating cancer.