Paclitaxel Enhances Carboplatin-DNA Adduct Formation and Cytotoxicity

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• 作者：Shuai Jiang ; Amy W. Pan ; Tzu-yin Lin ; Hongyong Zhang ; Michael Malfatti ; Kenneth Turteltaub ; Paul T. Henderson ; Chong-xian Pan
• 刊名：Chemical Research in Toxicology
• 出版年：2015
• 出版时间：December 21, 2015
• 年：2015
• 卷：28
• 期：12
• 页码：2250-2252
• 全文大小：187K
• ISSN：1520-5010

文摘

This rapid report focuses on the pharmacodynamic mechanism of the carboplatin/paclitaxel combination and correlates it with its cytotoxicity. Consistent with the synergistic to additive antitumor activity (the combination index ranging from 0.53 to 0.94), cells exposed to this combination had significantly increased carboplatin-DNA adduct formation when compared to that of carboplatin alone (450 卤 30 versus 320 卤 120 adducts per 10⁸ nucleotides at 2 h, p = 0.004). Removal of paclitaxel increased the repair of carboplatin-DNA adducts: 39.4 versus 33.1 adducts per 10⁸ nucleotides per hour in carboplatin alone (p = 0.021). This rapid report provides the first pharmacodynamics data to support the use of carboplatin/paclitaxel combination in the clinic.