The therapeutic efficacy of S-1 against orthotopically implanted human pleural mesothelioma cells in severe combined immunodeficient mice.
The therapeutic efficacy of S-1 against orthotopically implanted human pleural mesothelioma cells in severe combined immunodeficient mice.
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DOI：
10.1007/s00280-010-1503-x
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发表时间：
2011-08
影响因子：
3
通讯作者：
Sone, Saburo
中科院分区：
文献类型：
--
作者：
Trung The Van;Hanibuchi, Masaki;Kakiuchi, Soji;Sato, Seidai;Kuramoto, Takuya;Goto, Hisatsugu;Mitsuhashi, Atsushi;Nishioka, Yasuhiko;Akiyama, Shin-ichi;Sone, Saburo
恶性胸膜间皮瘤（MPM）是一种高度致命的肿瘤。 S-1 是一种基于 5-氟尿嘧啶 (5-FU) 生物活性调节的新型口服抗肿瘤药。本研究旨在探讨 S-1 对 MPM 的临床前治疗效果。我们使用了三种人类 MPM 细胞系：Y-MESO-14、NCI-H290 和 MSTO-211H。通过MTT法测定人MPM细胞的体外增殖。将人 MPM 细胞原位植入 SCID 小鼠胸腔。用S-1或载体治疗荷瘤小鼠。 5-FU和5-氯-2,4-二羟基吡啶(CDHP)的组合在体外抑制MPM细胞增殖方面比单独使用5-FU更有效。这种组合在 Y-MESO-14 细胞中最有效，该细胞共表达高蛋白水平的二氢嘧啶脱氢酶 (DPD) 和胸苷磷酸化酶 (TP)。体内数据显示，S-1 治疗显着减少了 Y-MESO-14 细胞产生的胸部肿瘤和胸腔积液。此外，S-1 治疗延长了携带 Y-MESO-14 细胞的 SCID 小鼠的存活率。我们证明 S-1 可有效抑制 MPM 细胞的增殖，特别是 DPD 和 TP 表达，表明 S-1 可能对控制 MPM 具有治疗效果。
Malignant pleural mesothelioma (MPM) is a highly lethal neoplasm. S-1 has been developed as a novel oral antineoplastic agent based on the modulation of 5-fluorouracil (5-FU) bioactivity. This study was conducted to investigate the preclinical therapeutic effect of S-1 on MPM. We used three human MPM cell lines, Y-MESO-14, NCI-H290 and MSTO-211H. In vitro proliferation of human MPM cells was determined by MTT assay. Human MPM cells were orthotopically implanted into thoracic cavity of SCID mice. Tumor-bearing mice were treated with S-1 or vehicle. The combination of 5-FU and 5-chloro-2,4-dihydroxypyridine (CDHP) was more effective than 5-FU alone in inhibiting MPM cell proliferation in vitro. This combination was most effective in Y-MESO-14 cells, which co-expressed high protein level of dihydropyrimidine dehydrogenase (DPD) and thymidine phosphorylase (TP). In vivo data showed that treatment with S-1 significantly reduced thoracic tumors and pleural effusion produced by Y-MESO-14 cells. Moreover, treatment with S-1 prolonged the survival of Y-MESO-14 cell-bearing SCID mice. We demonstrated that S-1 was effective for inhibiting the proliferation of MPM cells, particularly with both DPD and TP expressions, suggesting that S-1 might be therapeutically effective for control of MPM.
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