Targeting beta1 integrin restores sensitivity to docetaxel of esophageal squamous cell carcinoma.
Esophageal squamous cell carcinoma (ESCC) is a common and highly fatal cancer in Japan. Systemic chemotherapy is used, but some tumors show resistance to it. The mechanisms of tumor resistance to chemotherapy remain largely unknown. We determined the chemosensitivity of 15 ESCC cell lines (TE-1-5, TE-8-15, KYSE140 and KYSE150) to docetaxel by clonogenic and MTT assays. We used cDNA microarray analysis and quantitative RT-PCR to determine which genes might determine resistance to docetaxel. Small interfering RNA (siRNA) was used to suppress gene expression and its effect on the chemosensitivity of the cell was determined. The cell line with the most resistance to docetaxel was TE-2. Using microarray analysis, we identified beta1 integrin (ITGB1) to be overexpressed in this cell line. Higher expression of ITGB1 mRNA was significantly associated with docetaxel resistance (n=15, r2=0.66, P=0.0110). Suppression of ITGB1 expression using siRNA sensitized the TE-2 cells to docetaxel. These data suggest that overexpression of ITGB1 may be related to resistance to chemotherapy and that targeting ITGB1, particularly in patients on docetaxel therapy, may enhance the effect of chemotherapy in patients with ESCC.
Mori
Ryota
R
Nagoya City University Graduate School of Medical Sciences, Oncology, Immunology and Surgery, Nagoya 467-8601, Japan.
Ishiguro
Hideyuki
H
Kuwabara
Yoshiyuki
Y
Kimura
Masahiro
M
Mitsui
Akira
A
Tomoda
Keisuke
K
Mori
Yoichiro
Y
Ogawa
Ryo
R
Katada
Takeyasu
T
Harata
Koshiro
K
Fujii
Yoshitaka
Y
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020128:Inhibitory Concentration 50; D019012:Integrin beta1 / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043823:Taxoids / Q000494:pharmacology*
D000970:Antineoplastic Agents; D019012:Integrin beta1; D034741:RNA, Small Interfering; D043823:Taxoids; D000077143:Docetaxel