Expression of caveolin-1 and its correlation with cisplatin sensitivity in oral squamous cell carcinoma.
OBJECTIVE
Cisplatin (CDDP) is widely used for chemotherapy of oral squamous cell carcinoma (OSCC). However, the mechanism of resistance to CDDP is unclear. Recently, caveolin-1 was identified as being associated with both metastasis and multidrug resistance. In the present study, we showed that caveolin-1 expression is significantly related to chemosensitivity in OSCC.


METHODS
We established a CDDP-resistant cell line, H-1R, from the parental OSCC cell line, H-1. Caveolin-1 expression was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) in both cell lines. We analyzed expression of caveolin-1 in 30 OSCC biopsy specimens and investigated the relationship between expression of caveolin-1 and patients' clinicopathological parameters and chemotherapeutic responses.


RESULTS
The 3-(3,4-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that H-1R has a ten-times greater resistance to CDDP than H-1 has. The level of caveolin-1 expression in H-1R was significantly decreased in comparison with that in H-1 by real-time RT-PCR analysis. Positive caveolin-1 immunostaining correlated positively with a complete response (16/20, 80.0%). However, negative immunostaining was found in 6/7 (85.7%) cases with no response. Positive immunohistochemical staining of caveolin-1 correlated positively with chemosensitivity to CDDP-based combination chemotherapy (P=0.02).


CONCLUSIONS
These results suggest that overexpression of the caveolin-1 gene may provide novel diagnostic markers associated with CDDP sensitivity in OSCC.
Nakatani
Ken
K
Department of Oral and Maxillofacial Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-8509, Japan. n-gen@wakayama-med.ac.jp
Wada
Takeshi
T
Nakamura
Megumi
M
Uzawa
Katsuhiro
K
Tanzawa
Hideki
H
Fujita
Shigeyuki
S
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D051242:Caveolin 1; D022461:Caveolins / Q000235:genetics*; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015870:Gene Expression; D005887:Gingival Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D017663:Peplomycin / Q000008:administration & dosage; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014162:Transfection; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000008:administration & dosage
D014408:Biomarkers, Tumor; C495540:CAV1 protein, human; D051242:Caveolin 1; D022461:Caveolins; D012333:RNA, Messenger; D017663:Peplomycin; D014747:Vinblastine; D002945:Cisplatin