Role of ABCB1 and ABCG2 in the multidrug resistance of hypopharyngeal carcinoma FaDu cell line
10.3760/cma.j.issn.1673-0860.2012.04.009
- VernacularTitle:多药耐药基因ABCB1和ABCG2在下咽癌FaDu细胞多药耐药中的研究
- Author:
Ju-Ke MA
1
;
Su-Mei LU
;
Liang YU
;
Jia-Jun TIAN
;
Jian-Feng LI
;
Hai-Bo WANG
;
Wei XU
Author Information
1. 山东大学附属省立医院
- Keywords:
Hypopharyngeal neoplasms;
P-Glycoprotein;
Neoplasm proteins;
ATP binding cassette transporters;
Drug resistance,multiple;
Tumor cells,cultured
- From:
Chinese Journal of Otorhinolaryngology Head and Neck Surgery
2012;47(4):305-310
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the expression of multidrug resistance gene ABCB1 and ABCG2 in FaDu cells (human hypopharyngeal carcinoma cell line) and the multidrug resistance (MDR) cell lines FaDu/T transformed from FaDu cells by taxol and underlying mechanisms of MDR.Methods The multidrug resistance sensitivities of FaDu and FaDu/T to cisplatin (DDP),5-fluorouracil (5-FU),doxorubicin (Dox),and vincristine (VCR) were examined by methyl-thiazolyl-tetrazolium (MTF) assay.The mRNA and protein expressions of multidrug resistance genes ABCB1 and ABCG2 were analysed with RT-PCR,Western blot and laser confocal microscopy. JNK signal proteins were detected through Western blot.Results The multidrug resistance of FaDu/T cells to Taxol,DDP,5-FU,ADM and VCR was more than that of FaDu cells.The expression of ABCB1 in FaDu/T cells was significantly higher than that in FaDu cells (t =22.42,P ＜ 0.05 ),but the expression of ABCG2 in FaDu/T cells was significantly lower than that in FaDu cells (t =10.06,P ＜0.05).JNK signal was inhibited in FaDu or FaDu/T cells and the inhibited JNK was reactivated by taxol or anisomycin (an activator for MAPK signal transduction pathways ).Anisomycin down-regulated the expression of ABCB1 (F =33.72,P ＜0.05 ) and up-regulated the expression of ABCG2 (F=220.16,P ＜0.05) in FaDu/T cells,but not in FaDu/T cells pretreated by JNK inhibitor SP600125 (P ＞0.05).Conclusion The overexpression of ABCB1 and the down-regulation of ABCG2 in FaDu/T cells were the main features of MDR in hypopharyngeal carcinomas, in which JNK signal transduction pathways could play an important role.
