Interaction between novel anticancer agents and radiation in non-small cell lung cancer cell lines
Interaction between novel anticancer agents and radiation in non-small cell lung cancer cell lines
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DOI：
10.1016/s0169-5002(00)00247-6
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发表时间：
2001-07-01
期刊：
影响因子：
5.3
通讯作者：
Ardizzoni, A
中科院分区：
文献类型：
--
作者：
Loprevite, M;Favoni, RE;Ardizzoni, A
综合化疗和放射治疗是治疗局部晚期不能手术的非小细胞肺癌的标准做法。为了评价第三代化疗药物与放射治疗非小细胞肺癌(NSCLC)的生物相互作用，我们在肺癌细胞株中检测了几种不同的药物(紫杉醇、多西紫杉醇、吉西他滨、拓扑替康、SN-38和顺铂)联合放射治疗的效果。用半自动比色法测定药物浓度(0.001~100um)和辐射剂量(100~400cGy)作用48h、72h和96h后细胞对化疗药物的敏感性。所用细胞系为腺癌(ADK)A-549和鳞状细胞癌(SCC)LX-I。在照射前74、12和0h用抗癌药物对细胞进行预处理。细胞周期分析采用细胞荧光法。吉西他滨、拓扑替康或紫杉醇分别可引起明显的S期阻滞和G(2)/M期阻滞。只有在紫杉醇作用下，A-549细胞才出现细胞凋亡。尽管所有细胞株在化疗前诱导的细胞动力学变化模式相似，但腺癌A-549细胞株不受受试抗癌药物的联合放射增敏，而LX-1鳞癌细胞系在吉西他滨、SN-38、拓扑替康和顺铂作用下观察到协同作用。在我们的实验模型中，尽管紫杉醇具有良好的细胞周期效应，但并未发现其与放射治疗有协同作用。总而言之，观察到的协同作用似乎与剂量和时间无关，并且似乎与仅存在于鳞癌的组织亚型有关。在两种类型的细胞中测试所有新的试剂时，细胞周期的有利扰动是明显的，但不足以产生与辐射的协同作用。(C)2001爱思唯尔爱尔兰科学有限公司。保留所有权利。
Integration of chemotherapy and radiation is the standard practice in the management of locally advanced inoperable NSCLC. To assess the biological interaction between third generation chemotherapeutic agents and radiation in non-small cell lung cancer (NSCLC) in vitro, we tested a number of different drugs (paclitaxel, docetaxel, gemcitabine, topotecan, SN-38 and cisplatin) combined with radiation, in lung cancer cell lines. Cellular chemosensitivity was determined, using the semi-automated colorimetric MTT assay, after 48, 72 and 96 h of exposure to increasing drug concentrations, (0.001-100 muM) and radiation doses (100-400 cGy). Cell lines used were the adenocarcinoma (ADK), A-549, and the squamous-cell carcinoma (SCC), LX-I. Cells were pre-treated with anticancer agents at 74, 12 and 0 h before irradiation. Cytofluorimetric cell cycle analysis was performed. A significant S-phase block or a G(2)/M block was seen with gemcitabine and topotecan or paclitaxel pre-treatment, respectively. Apoptosis was seen only after paclitaxel exposure in the A-549 cell line. Despite a similar pattern of cell-kinetic changes induced by chemotherapy pre-treatment in all cell lines, the adenocarcinoma A-549 cell line was not radiosensitized by ally of the anticancer agents tested, whereas synergism was observed in the LX-1 squamous carcinoma cell line, when exposed to gemcitabine, SN-38, topotecan and cisplatin. Paclitaxel, despite a favourable cell cycle effect, was not found to be synergistic with radiotherapy in our experimental model. In conclusion, the observed synergism appears to be dose- and timing-independent and seems to be related to the histological subtype being present in SCC only. Favourable perturbation of the cell cycle is evident with all the new agents tested in both cell types, but was not sufficient to produce synergism with radiation. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.