4-Methylumbelliferone inhibits ovarian cancer growth by suppressing thymidine phosphorylase expression.
4-Methylumbelliferone inhibits ovarian cancer growth by suppressing thymidine phosphorylase expression.
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DOI：
10.1186/s13048-014-0094-2
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发表时间：
2014-10-11
影响因子：
4
通讯作者：
Mizunuma H
中科院分区：
文献类型：
--
作者：
Tamura R;Yokoyama Y;Yoshida H;Imaizumi T;Mizunuma H
4- methylumbellliferone （4-MU）是一种透明质酸（HA）合成抑制剂，具有抗肿瘤活性。然而，很少有研究关注其对卵巢癌的影响。本研究旨在探讨4-MU对卵巢癌的作用及其作用机制。本研究采用HRA人卵巢浆液腺癌细胞系。通过体外实验和体内大鼠腹膜癌模型研究4-MU对细胞增殖、迁移和侵袭的影响。采用定量逆转录-聚合酶链式反应（qRT-PCR）检测HRA细胞中HA合成酶（HAS）、CD44 HA受体、血管内皮生长因子（VEGF）和胸苷磷酸化酶（TP） mRNA的表达。4-MU给药可抑制腹膜肿瘤的生长，显著延长生存期。体外实验表明，4-MU抑制HRA细胞增殖呈剂量依赖性，但不影响HRA细胞的侵袭和迁移。4-MU显著降低HRA细胞中TP mRNA的表达。另一方面，由于HRA细胞中HAS2、CD44和VEGF内源性mRNA表达水平非常低，因此无法评估4-MU治疗的效果。提示4-MU通过抑制TP的表达发挥抗肿瘤作用。
4-Methylumbelliferone (4-MU), a hyaluronan (HA) synthesis inhibitor, has antitumor activity in cancer cells. However, few studies have focused on its effects on ovarian cancer. The aim of this study was to investigate the effects of 4-MU on ovarian cancer and to elucidate its mechanism of action. The HRA human ovarian serous adenocarcinoma cell line was used in this study. The effects of 4-MU on cell proliferation, migration, and invasion were determined by using in vitro assays as well as an in vivo rat peritoneal carcinomatosis model. The expression of HA synthase (HAS), CD44 HA receptor, vascular endothelial growth factor (VEGF), and thymidine phosphorylase (TP) mRNA in HRA cells was analyzed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). 4-MU administration inhibited the growth of peritoneal tumors and significantly prolonged survival. In vitro experiments showed that 4-MU inhibited HRA cell proliferation in a dose-dependent manner, while it did not affect HRA cell invasion and migration. 4-MU significantly decreased TP mRNA expression in HRA cells. On the other hand, since HAS2, CD44, and VEGF endogenous mRNA expression levels were very low in HRA cells, it was impossible to evaluate the effect of 4-MU treatment. These results suggest that 4-MU exerts its antitumor effect on ovarian cancer through suppressing TP expression.
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DOI：
10.1016/s0006-291x(03)00022-6
发表时间：
2003-02-14
影响因子：
3.1
作者：
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通讯作者：
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影响因子：
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影响因子：
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影响因子：
3.7
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