Kim Aeyung, Jung Ji-Yong, Son Minsik, Lee Sang-Han, Lim Jong-Seok, Chung An-Sik
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
Oncol Rep. 2008 Sep;20(3):557-65.
To assess the inhibitory effects of methylselenol on the invasion of murine B16F10 melanoma cells, we carried out in vivo and in vitro experiments using Se-methylselenocysteine (Se-MSC) and selenomethionine (SeMet), respectively. In an animal experiment, the supplementation of drinking water with Se-MSC (4 ppm Se) led to a significant increase in Se levels in the lung, liver and serum in mice. Mice given a mash diet or water supplemented with Se-MSC (2, 4 and 6 ppm Se in the mash diet, and 2 and 4 ppm Se in the drinking water) displayed an almost completely diminished pulmonary metastasis of B16F10 melanoma cells and an enhanced survival, compared to the control mice which were given a basal diet. Treatment with non-cytotoxic concentrations of SeMet (2.5, 5 and 10 microM plus 0.02 U/ml METase, methioninase) induced a substantial decrease in the expression of integrin alphavbeta3, the FN receptor and adhesion ability to vitronectin (VN) and fibronectin (FN) in B16F10 melanoma cells. Moreover, these compounds suppressed gelatinase activity, invasive ability and wound migration in the culture system. SeMet-METase prevented the conversion of pro-MMP-9 to its active form and decreased pro-MMP-2 activities in a zymogram. The pre-treatment of B16F10 melanoma cells with SeMet-METase led to a decrease in pulmonary metastasis and extended survival in mice injected with tumor cells. Collectively, our results indicate that integrin expression is crucial in promoting the metastatic phenotype in murine B16F10 melanoma cells by supporting specific adhesive and invasive properties, suggesting that Se-MSC effectively reduces the metastasis of B16F10 melanoma cells as a nutritional adjuvant. Methylselenol may also contribute to the suppression of integrin expression.
为了评估甲基硒醇对小鼠B16F10黑色素瘤细胞侵袭的抑制作用，我们分别使用硒代甲基硒代半胱氨酸（Se-MSC）和硒代蛋氨酸（SeMet）进行了体内和体外实验。在动物实验中，给小鼠饮用含Se-MSC（4 ppm硒）的水导致小鼠肺、肝和血清中的硒水平显著升高。与给予基础饮食的对照小鼠相比，给予含Se-MSC（饲料中含2、4和6 ppm硒，饮水中含2和4 ppm硒）的饲料或水的小鼠，B16F10黑色素瘤细胞的肺转移几乎完全减少，生存期延长。用无细胞毒性浓度的SeMet（2.5、5和10 microM加0.02 U/ml METase，蛋氨酸酶）处理可使B16F10黑色素瘤细胞中整合素αvβ3、纤连蛋白受体的表达以及对玻连蛋白（VN）和纤连蛋白（FN）的黏附能力大幅降低。此外，这些化合物在培养系统中抑制了明胶酶活性、侵袭能力和伤口迁移。SeMet-METase在酶谱分析中阻止了前基质金属蛋白酶-9转化为其活性形式，并降低了前基质金属蛋白酶-2的活性。用SeMet-METase预处理B16F10黑色素瘤细胞可减少接种肿瘤细胞的小鼠的肺转移并延长生存期。总体而言，我们的结果表明，整合素表达通过支持特定的黏附和侵袭特性，在促进小鼠B16F10黑色素瘤细胞的转移表型中起关键作用，这表明Se-MSC作为营养佐剂可有效减少B16F10黑色素瘤细胞的转移。甲基硒醇也可能有助于抑制整合素表达。
