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多西他赛联合放疗对人头颈部癌细胞(ZMK-1)和宫颈鳞状癌细胞(CaSki)的影响。

Effects of docetaxel in combination with radiation on human head and neck cancer cells (ZMK-1) and cervical squamous cell carcinoma cells (CaSki ).

作者信息

Pradier O, Rave-Fränk M, Lehmann J, Lücke E, Boghun O, Hess C F, Schmidberger H

机构信息

Department of Radiotherapy and Radiation Oncology, University of Göttingen, Robert-Koch-Str. 40, D 37075 Göttingen, Germany.

出版信息

Int J Cancer. 2001 Mar 15;91(6):840-5. doi: 10.1002/1097-0215(200002)9999:9999<::aid-ijc1142>3.0.co;2-u.

Abstract

The purpose of this study was to determine, as we did for paclitaxel, the cytotoxic and radiosensitizing potential of docetaxel in human head and neck cancer cells (ZMK-1), and in cervical squamous cell carcinoma cells (CaSki). ZMK-1 cells were incubated with docetaxel for 3, 9 or 24 hr before irradiation and 24 hr after irradiation. CaSki cells were incubated with docetaxel 24 hr before and after irradiation. For ZMK-1 cells, the docetaxel concentrations (0.7, 0.7 and 0.35 nM) were determined to obtain approximately equivalent cell survival at the different incubation times (3, 9 and 24 hr, respectively). For CaSki cells, the necessary concentration of docetaxel was 0.07 nM. Radiation doses were given from 0 to 7 Gy. Cell survival was measured by a standard clonogenic assay after a 9-day incubation. Flow cytometry was used to measure the capacity of docetaxel to accumulate cells in the G2/M phase of the cell cycle. We observed a weak accumulation of cells in the G2/M phase for the ZMK-1 cells and a pronounced accumulation for CaSki cells. For docetaxel incubation before irradiation, the isoeffect enhancement ratios for ZMK-1 cells determined at the 37% survival level were 1.18, 2.01, and 2.40 for pre-incubation at 3, 9 and 24 hr, respectively; for CaSki cells the ratio was 1.44. For a docetaxel incubation of 24 hr after irradiation, the isoeffect enhancement ratios determined at the 37% survival level were 1.54 and 1.17 for the ZMK-1, and CaSki cells, respectively. A radiosensitizing effect of docetaxel could be demonstrated unambiguously in the two cell lines used. In contrast to our previously published results with paclitaxel, docetaxel seems to be a better radiosensitizer than paclitaxel.

摘要

本研究的目的是,如同我们对紫杉醇所做的那样,确定多西他赛在人头颈部癌细胞(ZMK-1)和宫颈鳞状细胞癌细胞(CaSki)中的细胞毒性和放射增敏潜力。在照射前3、9或24小时以及照射后24小时,将ZMK-1细胞与多西他赛一起孵育。在照射前后24小时,将CaSki细胞与多西他赛一起孵育。对于ZMK-1细胞,确定多西他赛浓度(分别为0.7、0.7和0.35 nM),以便在不同孵育时间(分别为3、9和24小时)获得大致相当的细胞存活率。对于CaSki细胞,多西他赛的必要浓度为0.07 nM。辐射剂量为0至7 Gy。在9天孵育后,通过标准克隆形成试验测量细胞存活率。使用流式细胞术测量多西他赛使细胞在细胞周期G2/M期积累的能力。我们观察到ZMK-1细胞在G2/M期有较弱的细胞积累,而CaSki细胞有明显的积累。对于照射前的多西他赛孵育,在37%存活水平下测定的ZMK-1细胞的等效效应增强率,在3、9和24小时预孵育时分别为1.18、2.01和2.40;对于CaSki细胞,该比率为1.44。对于照射后24小时的多西他赛孵育,在37%存活水平下测定的等效效应增强率,对于ZMK-1细胞和CaSki细胞分别为1.54和1.17。在所使用的两种细胞系中,可以明确证明多西他赛的放射增敏作用。与我们之前发表的关于紫杉醇的结果相反,多西他赛似乎是比紫杉醇更好的放射增敏剂。

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