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首页> 外文期刊>Redox Biology >The timing of caffeic acid treatment with cisplatin determines sensitization or resistance of ovarian carcinoma cell lines
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The timing of caffeic acid treatment with cisplatin determines sensitization or resistance of ovarian carcinoma cell lines

机译：顺铂处理咖啡酸的时机决定了卵巢癌细胞系的敏感性或耐药性

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Cisplatin is a widely used chemotherapeutic drug showing high efficiency in the treatment of primary tumors such as ovarian, testicular and cervical cancers. The major drawback of cisplatin is tumor resistance either acquired or intrinsic. Many mechanisms are involved in the resistance, among them is the Nrf2 pathway which regulates glutathione related enzymes. Caffeic acid, a non-toxic polyphenol which is abundant in many foods modulates glutathione S-transferase (GST) and glutathione reductase (GSR) activity, these enzymes were shown to be involved in resistance of cells towards cisplatin. Caffeic acid induces the Nrf2 pathway and can also inhibit the activity of GST and GSR.Our findings demonstrate that the co-treatment of cancer cells with cisplatin and caffeic acid can enhance cisplatin cytotoxicity and increases the amount of platinum bound to nuclear DNA. However, 6 h of pre incubation with caffeic acid prior to cisplatin treatment led to acquired resistance to cisplatin and reduced DNA binding.In conclusion, the enzyme inhibitory action of caffeic acid is dominant when the two agents are co-administered leading to increased cytotoxicity, and the Nrf2 induction is dominant when the cells are treated with caffeic acid prior to cisplatin treatment leading to resistance.The use of caffeic acid as adjuvant for cisplatin should be carefully examined due to different pharmacokinetic profiles of caffeic acid and cisplatin. Thus, it is questionable if the two agents can reach the tumors at the right time frame in vivo .
机译：顺铂是一种广泛使用的化学治疗药物，在治疗原发性肿瘤（例如卵巢癌，睾丸癌和宫颈癌）方面显示出高效率。顺铂的主要缺点是获得性或固有的肿瘤抵抗力。抗性涉及许多机制，其中包括调节谷胱甘肽相关酶的Nrf2途径。咖啡酸是一种无毒的多酚，在许多食品中含量很高，可调节谷胱甘肽S-转移酶（GST）和谷胱甘肽还原酶（GSR）的活性，这些酶被证明与细胞对顺铂的耐药性有关。咖啡酸诱导Nrf2途径，也可以抑制GST和GSR的活性。我们的研究结果表明，将癌细胞与顺铂和咖啡酸共同处理可以增强顺铂的细胞毒性，并增加与核DNA结合的铂的量。但是，在顺铂处理之前与咖啡酸预孵育6小时会导致获得的顺铂耐药性并降低DNA结合。总而言之，当两种药物共同使用时，咖啡酸的酶抑制作用占主导地位，导致细胞毒性增加，在顺铂处理之前先用咖啡酸处理细胞会导致耐药，而Nrf2诱导则占主导地位。由于咖啡酸和顺铂的药代动力学特性不同，应仔细研究使用咖啡酸作为顺铂的佐剂。因此，令人怀疑的是，这两种药物是否能够在正确的体内时间到达肿瘤。

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