评估药物转运蛋白对头颈部鳞状细胞癌多药耐药性的意义。
Evaluation of drug transporters' significance for multidrug resistance in head and neck squamous cell carcinoma.
机构信息
Department of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
出版信息
Head Neck. 2011 Jul;33(7):959-68. doi: 10.1002/hed.21559. Epub 2010 Aug 24.
BACKGROUND
Multidrug resistance (MDR) hampers chemotherapy in head and neck squamous cell carcinoma (HNSCC). There is little information about MDR mediating drug transporters in HNSCC.
METHODS
Nine HNSCC cell lines were characterized concerning drug transporter expression and susceptibility to cisplatin, paclitaxel, and 5-fluorouracil (5-FU) using a DNA microarray and proliferation assays. Three cells lines were precisely investigated for transporter expression using reverse transcriptase-polymerase chain reaction (RT-PCR) and drug resistance before and after simulated chemotherapies.
RESULTS
The cell lines differed in drug resistance and transporter expression. Cisplatin and paclitaxel resistances were inversely associated. Drugs rendered HNSCC cells resistant, cross-resistant, or cross-sensitive. Sensitivity changes were accompanied by transporter mRNA expression changes.
CONCLUSION
Paclitaxel was identified as a potent inducer of numerous drug transporters and phenotypic MDR in HNSCC. Thus, cytostatic susceptibility of HNSCC cannot exclusively be deduced from the expression of single transporters but more likely of the entire transportome and non-transporter modulators.
背景
多药耐药（MDR）会阻碍头颈部鳞状细胞癌（HNSCC）的化疗。关于 HNSCC 中 MDR 介导的药物转运蛋白的信息很少。
方法
使用 DNA 微阵列和增殖测定法，对 9 种 HNSCC 细胞系进行了药物转运蛋白表达和对顺铂、紫杉醇和 5-氟尿嘧啶（5-FU）敏感性的特征描述。使用逆转录-聚合酶链反应（RT-PCR）和模拟化疗前后的药物耐药性，对三种细胞系进行了转运蛋白表达的精确研究。
结果
细胞系在药物耐药性和转运蛋白表达方面存在差异。顺铂和紫杉醇耐药性呈负相关。药物使 HNSCC 细胞产生耐药性、交叉耐药性或交叉敏感性。敏感性变化伴随着转运体 mRNA 表达的变化。
结论
紫杉醇被鉴定为 HNSCC 中多种药物转运蛋白和表型 MDR 的有效诱导剂。因此，HNSCC 的细胞抑制敏感性不能仅从单个转运体的表达来推断，而更可能来自整个转运组和非转运体调节剂。
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