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口腔鳞状细胞癌中小窝蛋白-1的表达及其与顺铂敏感性的相关性

Expression of caveolin-1 and its correlation with cisplatin sensitivity in oral squamous cell carcinoma.

作者信息

Nakatani Ken, Wada Takeshi, Nakamura Megumi, Uzawa Katsuhiro, Tanzawa Hideki, Fujita Shigeyuki

机构信息

Department of Oral and Maxillofacial Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-8509, Japan.

出版信息

J Cancer Res Clin Oncol. 2005 Jul;131(7):445-52. doi: 10.1007/s00432-004-0662-8. Epub 2005 Apr 26.

Abstract

PURPOSE

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.

摘要

目的

顺铂(CDDP)广泛用于口腔鳞状细胞癌(OSCC)的化疗。然而,对CDDP耐药的机制尚不清楚。最近,小窝蛋白-1被确定与转移和多药耐药均有关联。在本研究中,我们发现小窝蛋白-1的表达与OSCC的化疗敏感性显著相关。

方法

我们从亲本OSCC细胞系H-1建立了一个对CDDP耐药的细胞系H-1R。通过逆转录聚合酶链反应(RT-PCR)测定两个细胞系中小窝蛋白-1的表达。我们分析了30例OSCC活检标本中小窝蛋白-1的表达,并研究了小窝蛋白-1的表达与患者临床病理参数及化疗反应之间的关系。

结果

3-(3,4-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)试验表明,H-1R对CDDP的耐药性是H-1的10倍。实时RT-PCR分析显示,与H-1相比,H-1R中小窝蛋白-1的表达水平显著降低。小窝蛋白-1免疫染色阳性与完全缓解呈正相关(16/20,80.0%)。然而,在6/7(85.7%)无反应的病例中发现免疫染色阴性。小窝蛋白-1的阳性免疫组化染色与基于CDDP的联合化疗的化疗敏感性呈正相关(P=0.02)。

结论

这些结果表明,小窝蛋白-1基因的过表达可能为OSCC中与CDDP敏感性相关的新型诊断标志物。

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