Evaluation of drug transporters' significance for multidrug resistance in head and neck squamous cell carcinoma.
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.


CONCLUSIONS
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.
Theile
Dirk
D
Department of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
Ketabi-Kiyanvash
Nahal
N
Herold-Mende
Christel
C
Dyckhoff
Gerhardt
G
Efferth
Thomas
T
Bertholet
Vincent
V
Haefeli
Walter Emil
WE
Weiss
Johanna
J
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002945:Cisplatin / Q000627:therapeutic use; D054697:Cytostatic Agents / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005472:Fluorouracil / Q000627:therapeutic use; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D026901:Membrane Transport Proteins / Q000502:physiology*; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D017239:Paclitaxel / Q000627:therapeutic use; D000077195:Squamous Cell Carcinoma of Head and Neck
D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D002945:Cisplatin; D054697:Cytostatic Agents; D005472:Fluorouracil; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D017239:Paclitaxel