Nakatani Ken, Wada Takeshi, Nakamura Megumi, Uzawa Katsuhiro, Tanzawa Hideki, Fujita Shigeyuki
Department of Oral and Maxillofacial Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-8509, Japan.
J Cancer Res Clin Oncol. 2005 Jul;131(7):445-52. doi: 10.1007/s00432-004-0662-8. Epub 2005 Apr 26.
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.
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.
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).
These results suggest that overexpression of the caveolin-1 gene may provide novel diagnostic markers associated with CDDP sensitivity in OSCC.
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。
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。
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)。
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。