Docetaxel associated pathways in cisplatin resistant head and neck squamous cell carcinoma: a pilot study.
OBJECTIVE
This is a pilot study to identify changes in gene and protein expressions after treatment with docetaxel in cisplatin-resistant head and neck squamous cell carcinoma (HNSCC).


METHODS
Two cisplatin-resistant HNSCC cell lines, HN30 and HN12, were treated with either docetaxel or cisplatin. After 48 hours, differential gene expression between the two treatment groups (docetaxel-treated cells and cisplatin-treated cells) was analyzed using cDNA microarray. Differential protein expression between these two treatment groups was determined using PowerBlot and Western Blot analysis


RESULTS
A total of 150 genes and proteins were found to have differential expression patterns in HNSCC after treatment with docetaxel versus cisplatin. Many of these differentially expressed genes and proteins were involved in the cell cycle (decreased E2F), apoptosis (increased bax), angiogenesis (increased thrombospondin), and signal transduction (decreased epidermoid growth factor receptor) regulatory pathways.


CONCLUSIONS
Gene and protein expression are different and distinct between cells treated with docetaxel and cells treated with cisplatin. This finding provides evidence that different molecular pathways leading to cell death are targeted by docetaxel and cisplatin. Future studies focusing on these differentially expressed genes and proteins may improve our understanding, at the molecular level, of the mechanisms responsible for docetaxel-induced apoptosis in cisplatin-resistant HNSCC. Furthermore, these differentially expressed genes and proteins can be exploited as useful surrogate endpoint biomarkers in future clinical trials using docetaxel.
Yoo
George H
GH
Department of Otolaryngology-Head and Neck Surgery, Wayne State University and Karmanos Cancer Institute, Detroit, Michigan 48201, USA.
Lin
Ho-Sheng
HS
Iskander
Andrew J
AJ
Piechocki
Marie P
MP
Oliver
Jeffery
J
Kewson
Danny
D
Lonardo
Fulvio
F
Tainsky
Michael A
MA
Kim
Hyeong-Reh
HR
Kim
Harold
H
Ensley
John F
JF
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use*; D004273:DNA, Neoplasm / Q000235:genetics; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology*; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D010865:Pilot Projects; D015398:Signal Transduction / Q000187:drug effects; D043823:Taxoids / Q000627:therapeutic use*; D019699:Thrombospondins / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D043823:Taxoids; D019699:Thrombospondins; D051028:bcl-2-Associated X Protein; D000077143:Docetaxel; D002945:Cisplatin