Jiang Shuai, Pan Amy W, Lin Tzu-yin, Zhang Hongyong, Malfatti Michael, Turteltaub Kenneth, Henderson Paul T, Pan Chong-xian
Department of Internal Medicine, Division of Hematology and Oncology, University of California Davis , 4501 X Street, Room 3016, Sacramento, California 95817, United States.
Lawrence Livermore National Laboratory , P.O. Box 808, Livermore, California 94551-0808, United States.
Chem Res Toxicol. 2015 Dec 21;28(12):2250-2. doi: 10.1021/acs.chemrestox.5b00422. Epub 2015 Nov 11.
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 ± 30 versus 320 ± 120 adducts per 10(8) nucleotides at 2 h, p = 0.004). Removal of paclitaxel increased the repair of carboplatin-DNA adducts: 39.4 versus 33.1 adducts per 10(8) 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.
本快速报告聚焦于卡铂/紫杉醇联合用药的药效学机制，并将其与细胞毒性相关联。与协同至相加的抗肿瘤活性一致（联合指数范围为0.53至0.94），与单独使用卡铂相比，暴露于该联合用药的细胞中卡铂-DNA加合物的形成显著增加（2小时时每10⁸个核苷酸的加合物数量分别为450±30和320±120，p = 0.004）。去除紫杉醇会增加卡铂-DNA加合物的修复：单独使用卡铂时每小时每10⁸个核苷酸的加合物数量分别为39.4和33.1（p = 0.021）。本快速报告提供了首个药效学数据，以支持卡铂/紫杉醇联合用药在临床上的应用。
