Nakajima Yuichi, Haraguchi Misako, Furukawa Tatsuhiko, Yamamoto Masatatsu, Nakanishi Hayao, Tatematsu Masae, Akiyama Shin-ichi
Department of Molecular Oncology, Field of Oncology, Course of Advanced Therapeutics,Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, Japan.
Int J Cancer. 2006 Oct 1;119(7):1710-6. doi: 10.1002/ijc.22014.
Thymidine phosphorylase (TP), an enzyme involved in pyrimidine metabolism, is identical with an angiogenic factor, platelet-derived endothelial cell growth factor. 2-Deoxy-D-ribose (D-dRib), the degradation product of thymidine generated by TP activity, has been suggested to be a downstream mediator of TP function. 2-Deoxy-L-ribose (L-dRib), a stereoisomer of D-dRib, inhibited the promotion of angiogenesis, tumor growth and metastasis by TP. In our study, we have shown that nude mice inoculated with TP-overexpressing KB/TP cells had shorter survival times than those injected with control KB/CV cells. KB/TP tumors were also more highly invasive than KB/CV tumors in mice. The expression levels of matrix metalloproteinase (MMP)-9 in KB/TP tumors were significantly higher than those in KB/CV tumors. L-dRib and a TP inhibitior, TPI, extended the survival period of KB/TP tumor-bearing mice. L-dRib also reduced MMP-9 mRNA levels in KB/TP tumors. Furthermore, L-dRib suppressed the mRNA level of MMP-9 in cultured KB/TP cells, and the invasive activity of the cells. L-dRib may be useful for the suppression of invasion of TP-expressing tumor cells.
胸苷磷酸化酶（TP）是一种参与嘧啶代谢的酶，与血管生成因子血小板衍生内皮细胞生长因子相同。2-脱氧-D-核糖（D-dRib）是TP活性产生的胸苷降解产物，被认为是TP功能的下游介质。2-脱氧-L-核糖（L-dRib）是D-dRib的立体异构体，可抑制TP对血管生成、肿瘤生长和转移的促进作用。在我们的研究中，我们发现接种过表达TP的KB/TP细胞的裸鼠比注射对照KB/CV细胞的裸鼠存活时间更短。KB/TP肿瘤在小鼠中的侵袭性也比KB/CV肿瘤更强。KB/TP肿瘤中基质金属蛋白酶（MMP）-9的表达水平显著高于KB/CV肿瘤。L-dRib和一种TP抑制剂TPI延长了荷KB/TP肿瘤小鼠的生存期。L-dRib还降低了KB/TP肿瘤中MMP-9的mRNA水平。此外，L-dRib抑制了培养的KB/TP细胞中MMP-9的mRNA水平以及细胞的侵袭活性。L-dRib可能有助于抑制表达TP的肿瘤细胞的侵袭。
