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5-氟尿嘧啶和顺铂对宫颈癌细胞的体外协同作用分析。

Analysis of the in vitro synergistic effect of 5-fluorouracil and cisplatin on cervical carcinoma cells.

作者信息

Yim E-K, Lee S B, Lee K-H, Kim C-J, Park J-S

机构信息

Department of Obstetrics and Gynecology, Catholic University Medical College, 505 Banpo-dong, Seocho-gu, Seoul 137-040, Republic of Korea.

出版信息

Int J Gynecol Cancer. 2006 May-Jun;16(3):1321-9. doi: 10.1111/j.1525-1438.2006.00551.x.

Abstract

5-Fluorouracil (5-FU) is currently being used as an anticancer drug to reduce tumor bulk in order to increase the operability rate and postoperative survival in patients with cervical cancer, which has been combined with cisplatin (CP) because of its superior activities observed in human carcinoma cells. However, the combined anticancer effect of 5-FU and CP in cervical carcinoma cells is poorly understood. Therefore, we conducted a study to investigate whether anticancer drugs 5-FU and CP may exhibit the combined antiproliferative effect in cervical carcinoma cells. Using proteomics analysis, including two-dimensional gel electrophoresis and matrix assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS), we investigated the antiproliferative effect-related proteins after treatment with 5-FU and/or CP. Our experiments showed that the combination of 5-FU and CP engaged both the apoptotic pathways: the membrane death receptor-mediated apoptosis pathway and the mitochondrial apoptotic pathway. Moreover, the combination of 5-FU and CP resulted in remarkable increasing susceptibility to apoptosis. We suggest that the combination of 5-FU and CP suppresses the growth of cervical carcinoma cells by synergistic effect with the induction of apoptosis. In vitro synergistic effect of 5-FU and CP supports the basis of the clinical application of the combination chemotherapy to the patients with cervical cancer.

摘要

5-氟尿嘧啶(5-FU)目前被用作抗癌药物以减小肿瘤体积,从而提高宫颈癌患者的手术切除率和术后生存率。由于在人类癌细胞中观察到其具有卓越活性,5-FU已与顺铂(CP)联合使用。然而,5-FU与CP在宫颈癌细胞中的联合抗癌作用尚不清楚。因此,我们开展了一项研究,以探究抗癌药物5-FU和CP在宫颈癌细胞中是否可能表现出联合抗增殖作用。我们利用蛋白质组学分析,包括二维凝胶电泳和基质辅助激光解吸/电离飞行时间质谱(MALDI-TOF-MS),研究了用5-FU和/或CP处理后与抗增殖作用相关的蛋白质。我们的实验表明,5-FU与CP的联合作用激活了两条凋亡途径:膜死亡受体介导的凋亡途径和线粒体凋亡途径。此外,5-FU与CP的联合作用导致对凋亡的敏感性显著增加。我们认为,5-FU与CP的联合作用通过协同诱导凋亡来抑制宫颈癌细胞的生长。5-FU与CP的体外协同作用为联合化疗在宫颈癌患者中的临床应用提供了依据。

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