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5-氮杂-2'-脱氧胞苷增强前列腺癌DU145细胞对顺铂的敏感性。

Enhanced sensitivity of prostate cancer DU145 cells to cisplatinum by 5-aza-2'-deoxycytidine.

作者信息

Fang Xiaolei, Zheng Chengyun, Liu Zhaoxu, Ekman Peter, Xu Dawei

机构信息

Department of Urology, Karolinska Institute and Hospital, SE-171 76 Stockholm, Sweden.

出版信息

Oncol Rep. 2004 Sep;12(3):523-6.

Abstract

During the oncopathogenic process aberrant DNA methylation frequently occurs, leading to silencing of sets of genes involved in cell cycle and apoptosis control pathways and other important biological functions. Targeting such a change has been suggested as a novel strategy for cancer prevention and therapy. In the present study, we examined whether suppression of DNA methylation was capable of enhancing sensitivity of prostate cancer DU145 cells to cisplatinum. 5-aza-2'-deoxycytidine (5-aza), a specific DNA methylation inhibitor, when added into DU145 cell culture alone, did not induce significant apoptosis. However, a combination of 5-aza with the chemotherapeutic agent cisplatinum showed great synergy in triggering apoptotic death of DU145 cells. The present finding provides a rationale to evaluate therapeutic effects of the DNA methylation inhibition and chemotherapy in patients with prostate cancer.

摘要

在肿瘤发生过程中,异常的DNA甲基化频繁发生,导致参与细胞周期和凋亡控制途径以及其他重要生物学功能的基因沉默。针对这种变化已被提议作为癌症预防和治疗的新策略。在本研究中,我们检测了DNA甲基化抑制是否能够增强前列腺癌DU145细胞对顺铂的敏感性。5-氮杂-2'-脱氧胞苷(5-aza),一种特异性DNA甲基化抑制剂,单独添加到DU145细胞培养物中时,不会诱导明显的凋亡。然而,5-aza与化疗药物顺铂联合使用在触发DU145细胞凋亡死亡方面显示出极大的协同作用。本研究结果为评估DNA甲基化抑制和化疗对前列腺癌患者的治疗效果提供了理论依据。

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