头颈部鳞状细胞癌中多西紫杉醇诱导的多药耐药的 microRNA 表达谱。

MicroRNA expression profiles of head and neck squamous cell carcinoma with docetaxel-induced multidrug resistance.

机构信息

Department of Otolaryngology-Head and Neck Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.

出版信息

Head Neck. 2011 Jun;33(6):786-91. doi: 10.1002/hed.21540. Epub 2010 Nov 29.

DOI:10.1002/hed.21540

PMID:21560177

Abstract

BACKGROUND

The purpose of this study was to investigate the potential role of variable microRNA (miRNA) expression in the development of multidrug resistance (MDR) in head and neck cancer.

METHODS

Head and neck squamous cell carcinoma cell lines UMSCC-1 and SQ20B were treated with docetaxel at increasing concentrations to develop resistant cell lines. Parental and resistant cells were treated with cisplatin, 5-fluorouracil, paclitaxel, methotrexate, and doxorubicin to confirm cross-resistance. The miRNA pattern of resistant cells was then compared with their parental cells.

RESULTS

Docetaxel treatment successfully induced resistance primarily and induced multidrug cross-resistance. Resistant cells showed significant downregulation of miR-100, miR-130a, and miR-197 and upregulation in miR-101, miR-181b, miR-181d, and miR-195 expression when compared with their parent cells (p < .01). Real-time polymerase chain reaction (PCR) analysis confirmed statistically significant downregulation in miR-100 and miR-130a and upregulation in miR-181d expression (p < .001).

CONCLUSION

Alterations in miRNA expression has direct relationship to MDR in head and neck cancer and may serve as biomolecular targets for reversal of MDR.

摘要

背景

本研究旨在探讨可变微小 RNA（miRNA）表达在头颈部癌症多药耐药（MDR）发展中的潜在作用。

方法

用多西紫杉醇处理头颈部鳞状细胞癌细胞系 UMSCC-1 和 SQ20B 以开发耐药细胞系。用顺铂、5-氟尿嘧啶、紫杉醇、甲氨蝶呤和阿霉素处理亲本和耐药细胞，以确认交叉耐药性。然后将耐药细胞的 miRNA 模式与其亲本细胞进行比较。

结果

多西紫杉醇治疗成功地主要诱导了耐药性，并诱导了多药交叉耐药性。与亲本细胞相比，耐药细胞的 miR-100、miR-130a 和 miR-197 表达显著下调，而 miR-101、miR-181b、miR-181d 和 miR-195 表达上调（p<0.01）。实时聚合酶链反应（PCR）分析证实 miR-100 和 miR-130a 的表达显著下调，miR-181d 的表达上调（p<0.001）。