Combined paclitaxel, cisplatin and fluorouracil therapy enhances ionizing radiation effects, inhibits migration and induces G0/G1 cell cycle arrest and apoptosis in oral carcinoma cell lines
Combined paclitaxel, cisplatin and fluorouracil therapy enhances ionizing radiation effects, inhibits migration and induces G0/G1 cell cycle arrest and apoptosis in oral carcinoma cell lines
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DOI：
10.3892/ol.2015.3458
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发表时间：
2015-09-01
期刊：
影响因子：
2.9
通讯作者：
Guerra, Eliete Neves Silva
中科院分区：
文献类型：
--
作者：
Elias, Silvia Taveira;Borges, Gabriel Alvares;Guerra, Eliete Neves Silva
尽管紫杉醇（特别是紫杉醇）、顺铂和氟尿嘧啶（TPF）化疗已被批准用于治疗头颈部鳞状细胞癌（HNSCC），但关于这种新型药物联合的细胞机制知之甚少。为了研究这种新的治疗细胞的反应，本研究的目的是检查TPF在HNSCC细胞系中的细胞毒性作用与辐射相结合，分析其对细胞周期进程和细胞死亡的影响，并评估其改变细胞迁移的能力。使用MTT测定法来测定两种人HNSCC细胞系（FaDu和SCC-9）和一种角质形成细胞系（HaCaT）中TPF和顺铂处理后的细胞活力。同时分析TPF或顺铂与放疗的联合使用情况。流式细胞仪分析，以确定细胞周期分布，并验证诱导凋亡。还使用Transwell迁移试验评估了药物改变口腔癌细胞迁移的能力。结果表明，TPF和顺铂对所有细胞株均具有细胞毒作用，并能增强电离辐射的效应。FaDu细胞对两种处理显著更敏感，并且TPF对所有细胞的细胞毒性均大于顺铂。流式细胞仪分析显示，TPF增加了SCC-9细胞系中G 0/G1期的细胞数量，并表明细胞凋亡。Transwell实验结果表明TPF抑制口腔癌细胞系的迁移。本研究的结果表明，TPF功能在口腔癌细胞系通过增强电离辐射效应，诱导细胞周期停滞在G 0/G1和凋亡，除了抑制迁移。
Although taxels (in particular paclitaxel), cisplatin and fluorouracil (TPF) chemotherapy has been approved for use in the treatment of head and neck squamous cell carcinoma (HNSCC), little is known with regard to the cellular mechanisms of this novel drug association. In order to investigate the reaction of cells to this novel treatment, the present study aimed to examine the cytotoxic effect of TPF in HNSCC cell lines in combination with irradiation, to analyze its effect on cell cycle progression and cell death, and to evaluate its ability to alter cell migration. An MTT assay was used to determine cell viability following TPF and cisplatin treatments in two human HNSCC cell lines (FaDu and SCC-9) and one keratinocyte cell line (HaCaT). The concurrent use of TPF or cisplatin and irradiation was also analyzed. Flow cytometric analysis was utilized to determine the cell cycle distribution and to verify the induction of apoptosis. The capacity of the drugs to alter oral cancer cell migration was also evaluated using a Transwell migration assay. The results indicated that TPF and cisplatin were cytotoxic to all cell lines, and enhanced the effects of ionizing radiation. FaDu cells were significantly more sensitive to the two treatments, and TPF was more cytotoxic than cisplatin for all cells. Flow cytometric analysis revealed that TPF increased the number of cells in G0/G1 phase in the SCC-9 cell line, and indicated apoptotic cell death. The results of the Transwell assay demonstrated that TPF inhibited migration in oral carcinoma cell lines. The results of the present study indicated that TPF functions in oral carcinoma cell lines through the enhancement of ionizing radiation effects, inducing cell cycle arrest at G0/G1 and apoptosis, in addition to inhibiting migration.