4-methylumbelliferone, a hyaluronan synthase suppressor, enhances the anticancer activity of gemcitabine in human pancreatic cancer cells.
4-methylumbelliferone, a hyaluronan synthase suppressor, enhances the anticancer activity of gemcitabine in human pancreatic cancer cells.
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DOI：
10.1007/s00280-005-0016-5
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发表时间：
2006-01-01
影响因子：
3
通讯作者：
Sasaki, Mutsuo
中科院分区：
文献类型：
--
作者：
Nakazawa, Hideaki;Yoshihara, Shuichi;Sasaki, Mutsuo
透明质酸(HA)是一种普遍存在的细胞外基质的主要成分，是各种生理过程所必需的。它在生物屏障中扮演着非常重要的角色。我们先前报道了4-甲基伞形酮(MU)抑制培养的人皮肤成纤维细胞、马链球菌FM100和B16F10黑色素瘤细胞的HA合成和细胞周围HA基质的形成。我们推测，MU介导的抑制HA合成和细胞外HA基质形成将增加抗癌药物的疗效。我们已经在体外用夹心结合蛋白实验和颗粒排斥实验证明，在人KP1-NL胰腺癌细胞中，MU分别抑制HA合成和细胞周围HA基质的形成。AlamarBlue实验显示，MU可增强吉西他滨对KP1-NL细胞的抗癌作用。在体内，MU和吉西他滨同时应用于患有严重联合免疫缺陷病(SCID)的荷瘤小鼠，比单独使用吉西他滨更能缩小原发和转移瘤的大小。这些数据有力地表明MU和吉西他滨联合应用对人胰腺癌细胞是有效的。MU可能具有作为化学增敏剂的潜力，可能为我们提供一种新的抗癌策略。
Hyaluronan (HA) is a ubiquitous, major component of the pericellular matrix and is necessary for various physiological processes. It plays a very important role in biological barriers. We previously reported that 4-methylumbelliferone (MU) inhibits HA synthesis and pericellular HA matrix formation in cultured human skin fibroblasts, Streptococcus equi FM100, and B16F10 melanoma cells. We hypothesized that MU-mediated inhibition of HA synthesis and pericellular HA matrix formation would increase the efficacy of anticancer drugs. We have already demonstrated in vitro, using a sandwich binding protein assay and a particle exclusion assay, that MU inhibits HA synthesis and formation of the pericellular HA matrix, respectively, in human KP1-NL pancreatic cancer cells. AlamarBlue assay revealed that the anticancer effect of gemcitabine in KP1-NL cells was increased by pretreatment with MU. In vivo simultaneous administration of MU and gemcitabine to tumor-bearing mice with severe combined immunodeficiency disease (SCID) decreased the size of the primary and metastatic tumors more than did gemcitabine alone. These data strongly suggest that a combination of MU and gemcitabine is effective against human pancreatic cancer cells. MU may have potential as a chemosensitizer and may provide us with a new anticancer strategy.