Department of Medical Oncology, University of Tokushima Graduate School, Tokushima, Japan.
Cancer Chemother Pharmacol. 2011 Aug;68(2):497-504. doi: 10.1007/s00280-010-1503-x. Epub 2010 Nov 16.
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.
恶性胸膜间皮瘤（MPM）是一种高度致命的肿瘤。S-1 是基于 5-氟尿嘧啶（5-FU）生物活性的调节而开发的新型口服抗肿瘤药物。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 MPM 细胞系，Y-MESO-14、NCI-H290 和 MSTO-211H。通过 MTT 测定法测定人 MPM 细胞的体外增殖。将人 MPM 细胞原位植入 SCID 小鼠的胸腔中。荷瘤小鼠用 S-1 或载体治疗。
5-FU 和 5-氯-2,4-二羟基吡啶（CDHP）的组合在体外抑制 MPM 细胞增殖的效果优于 5-FU 单独使用。这种组合在共表达高水平二氢嘧啶脱氢酶（DPD）和胸苷磷酸化酶（TP）的 Y-MESO-14 细胞中最有效。体内数据显示，S-1 治疗显著减少了 Y-MESO-14 细胞产生的胸腔肿瘤和胸腔积液。此外，S-1 治疗延长了 Y-MESO-14 细胞荷瘤 SCID 小鼠的生存时间。
我们证明 S-1 能有效抑制 MPM 细胞的增殖，特别是在 DPD 和 TP 表达的情况下，表明 S-1 可能对 MPM 的控制具有治疗效果。
