Montopoli M, Ragazzi E, Froldi G, Caparrotta L
Department of Pharmacology and Anaesthesiology, University of Padova, Padova, Italy.
Cell Prolif. 2009 Apr;42(2):195-206. doi: 10.1111/j.1365-2184.2009.00585.x. Epub 2009 Feb 18.
Alteration of appropriate cell-cycle progression and of closely related apoptotic process is a basic feature of tumour cells, and development of new tumour-targeted agents focus on apoptosis, either during cell-cycle arrest or following premature cell-cycle checkpoint exit. Increasingly, epidemiological and experimental studies suggest that curcumin protects against cancer, not only because of its well-known antioxidant properties, but also because it modulates intracellular signalling, which is related to cell proliferation and apoptosis. Cisplatin and oxaliplatin are first-line drugs in treatment of many types of epithelial cancer and their combination with other cytostatics are under investigation to limit their side effects and resistance to them.
The aim of this study was to evaluate effects of a combined treatment using curcumin with cisplatin or with oxaliplatin, in a human ovarian cancer cell line (2008) and in its cisplatin-resistant variant (C13).
Curcumin per se caused concentration-dependent (0.1-100 microm) and time-persistent (24-72 h) reduction in cell proliferation, as well as altered cell cycle parameters and induced apoptosis, in both cell lines. When carcinoma cells were simultaneously exposed to curcumin and to cisplatin or oxaliplatin (at concentrations lower than IC(50)) cell viability was reduced more than with single-drug treatment. Moreover, dose and time related effects of curcumin, when combined with platinum drugs, were linked to consistent reduction in cell cycling and increased apoptosis, in comparison with single-drug treatment. These effects were significant both in wild type and in cisplatin-resistant cells, indicating that curcumin was also able to increase sensitivity of resistant ovarian cancer cells to cisplatin.
The data suggests that curcumin is an interesting natural compound capable of limiting cell proliferation and possibly increasing clinical impact of platinum drugs, in ovarian cancer patients.
适当的细胞周期进程改变以及密切相关的凋亡过程改变是肿瘤细胞的基本特征，新型肿瘤靶向药物的研发聚焦于细胞周期阻滞期间或过早退出细胞周期检查点后的凋亡。越来越多的流行病学和实验研究表明，姜黄素预防癌症不仅因其众所周知的抗氧化特性，还因其调节与细胞增殖和凋亡相关的细胞内信号传导。顺铂和奥沙利铂是治疗多种上皮癌的一线药物，它们与其他细胞抑制剂联合使用正在进行研究，以限制其副作用和耐药性。
本研究的目的是评估姜黄素与顺铂或奥沙利铂联合治疗对人卵巢癌细胞系（2008）及其顺铂耐药变体（C13）的影响。
姜黄素本身在两种细胞系中均导致浓度依赖性（0.1 - 100微摩尔）和时间持续性（24 - 72小时）的细胞增殖减少，以及细胞周期参数改变和诱导凋亡。当癌细胞同时暴露于姜黄素和顺铂或奥沙利铂（浓度低于IC50）时，细胞活力比单药治疗降低得更多。此外，与单药治疗相比，姜黄素与铂类药物联合使用时的剂量和时间相关效应与细胞周期一致减少和凋亡增加有关。这些效应在野生型和顺铂耐药细胞中均显著，表明姜黄素还能够增加耐药卵巢癌细胞对顺铂的敏感性。
数据表明姜黄素是一种有趣的天然化合物，能够限制细胞增殖，并可能增加铂类药物对卵巢癌患者的临床疗效。
