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抗癌药物在低氧-低营养培养条件下对肝癌细胞的细胞毒性活性。

Cytotoxic activity of anticancer drugs on hepatocellular carcinoma cells in hypoxic-hyponutritional culture.

作者信息

Li Qiang, Zhu Lin-Zhong, Yang Ren-Jie, Zhu Xu

机构信息

1 Department of Interventional Radiology, Peking University Cancer Hospital, Beijing, China.

出版信息

Int Surg. 2014 Nov-Dec;99(6):745-52. doi: 10.9738/INTSURG-D-14-00073.1.

Abstract

To investigate which anticancer drugs and combination of dual drugs could further promote the inhibition of cell growth in vitro against HCC cell line (HepG2) in the hypoxic and hyponutritional culture medium (HHCM) mimicked the different scenarios of transcatheter arterial chemoembolization (TACE). The cells of hepatocellular carcinoma (HCC) treated by TACE suffered various hypoxia and hyponutrition. The cells were treated for 2 hours, 4 hours, 6 hours, and 24 hours, respectively, using 10 drugs including epirubicin (EPI), cisplatin (DDP), mitomycin-C (MMC), oxaliplatin (OXA), hydroxycamptothecin (HCPT), 5-fluorouracil (5-FU), gemcitabine (GEM), docetaxel (DTX), thiotepa (TSPA), and pemetrexed disodium (PEM) in 4 concentrations of HHCM (5%, 10%, 25%, and 50%, respectively) mimicking the scenario of TACE and were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cells treated with combinations of dual drugs for 24 hours were also tested. The sensitive drugs with inhibition rates more than 30% were EPI, MMC, HCPT, OXA, and PEM in 4 types of HHCMs. The sensitivity of the cells to treatment with drugs for 24 hours was significantly higher than the sensitivity of the cells to treatment with drugs for 2 hours in 5%, 10%, and 25% HHCM. The sensitivity of the combination of dual drugs was no more than the sensitivity of the single drug with higher sensitivity in 4 concentrations of HHCM. EPI, MMC, HCPT, OXA, and PEM exhibited cytotoxic activity against HepG2 cells in various hypoxia and hyponutrition states. Prolonging the time of exposure could increase the sensitivity of drug, and the combination of dual drugs cannot enhance the cytotoxic effect.

摘要

为了研究哪些抗癌药物及双药组合能在模拟经动脉化疗栓塞术(TACE)不同情况的低氧低营养培养基(HHCM)中进一步促进对肝癌细胞系(HepG2)体外生长的抑制作用。接受TACE治疗的肝细胞癌(HCC)细胞会经历各种缺氧和低营养状态。分别使用包括表柔比星(EPI)、顺铂(DDP)、丝裂霉素-C(MMC)、奥沙利铂(OXA)、羟基喜树碱(HCPT)、5-氟尿嘧啶(5-FU)、吉西他滨(GEM)、多西他赛(DTX)、噻替派(TSPA)和培美曲塞二钠(PEM)在内的10种药物,在模拟TACE情况的4种浓度(分别为5%、10%、25%和50%)的HHCM中对细胞进行2小时、4小时、6小时和24小时的处理,并使用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)法进行评估。还对用双药组合处理24小时的细胞进行了测试。在4种类型的HHCM中,抑制率超过30%的敏感药物为EPI、MMC、HCPT、OXA和PEM。在5%、10%和25%的HHCM中,细胞对药物处理24小时的敏感性显著高于对药物处理2小时时的敏感性。在4种浓度的HHCM中,双药组合的敏感性不超过具有较高敏感性的单药的敏感性。EPI、MMC、HCPT、OXA和PEM在各种缺氧和低营养状态下对HepG2细胞表现出细胞毒活性。延长暴露时间可增加药物敏感性,且双药组合不能增强细胞毒作用。

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