Nakamura Rika, Kuwabara Hiroko, Yoneda Masahiko, Yoshihara Shuichi, Ishikawa Takashi, Miura Tomisato, Nozaka Hiroyuki, Nanashima Naoki, Sato Tatsusuke, Nakamura Toshiya
Department of Medical Technology, Hirosaki University School of Health Sciences, 66-1 Hon-cho, Hirosaki 036-8564, Japan.
Cell Biol Int. 2007 Sep;31(9):1022-6. doi: 10.1016/j.cellbi.2007.03.016. Epub 2007 Mar 20.
OHK cells, a human lymphoma cell line, are known to produce large amounts of hyaluronan. We investigated the effect of 4-methylumbelliferone, an inhibitor of hyaluronan synthesis, on the activity of matrix metalloproteinases in OHK cells. Matrix metalloproteinase-9 was detected on gelatin zymography as the main metalloproteinase excreted into the medium of cultured OHK cells, and 4-methylumbelliferone added to the medium decreased the activity of the enzyme in a dose-dependent manner. Addition of Streptomyces hyaluronidase to the medium during cultivation did not decrease the enzyme activity. Reverse transcription-polymerase chain reaction revealed that 4-methylumbelliferone markedly decreased the level of mRNA for matrix metalloproteinase-9 in cultured OHK cells. A similar decrease of the activity of matrix metalloproteinase-9 by 4-methylumbelliferone was also observed in cultured human breast and colon carcinoma cells. These results suggest that 4-methylumbelliferone suppresses the expression of matrix metalloproteinase-9 in cultured cancer cells.
OHK细胞是一种人淋巴瘤细胞系，已知其能产生大量透明质酸。我们研究了透明质酸合成抑制剂4-甲基伞形酮对OHK细胞中基质金属蛋白酶活性的影响。在明胶酶谱法中检测到基质金属蛋白酶-9是分泌到培养的OHK细胞培养基中的主要金属蛋白酶，向培养基中添加4-甲基伞形酮可剂量依赖性地降低该酶的活性。在培养过程中向培养基中添加链霉菌透明质酸酶并不会降低酶活性。逆转录-聚合酶链反应显示，4-甲基伞形酮显著降低了培养的OHK细胞中基质金属蛋白酶-9的mRNA水平。在培养的人乳腺癌和结肠癌细胞中也观察到4-甲基伞形酮对基质金属蛋白酶-9活性有类似的降低作用。这些结果表明，4-甲基伞形酮可抑制培养的癌细胞中基质金属蛋白酶-9的表达。
