Establishment and characterization of a cisplatin-resistant oral squamous cell carcinoma cell line, H-1R.
Establishment and characterization of a cisplatin-resistant oral squamous cell carcinoma cell line, H-1R.
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DOI：
10.3892/or.14.5.1281
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发表时间：
2005-11
期刊：
影响因子：
4.2
通讯作者：
Megumi Nakamura;Ken Nakatani;K. Uzawa;K. Ono;H. Uesugi;K. Ogawara;M. Shiiba;H. Bukawa;H. Yokoe;T. Wada;S. Fujita;H. Tanzawa
中科院分区：
文献类型：
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作者：
Megumi Nakamura;Ken Nakatani;K. Uzawa;K. Ono;H. Uesugi;K. Ogawara;M. Shiiba;H. Bukawa;H. Yokoe;T. Wada;S. Fujita;H. Tanzawa
顺铂（Cisplatin，CDDP）是一种广泛应用于多种恶性肿瘤的有效化疗药物。然而，对CDDP的耐药机制仍不清楚。为了研究其分子机制，我们从来源于下牙龈中分化鳞状细胞癌的CDDP敏感细胞系（H-1）中建立了CDDP耐药细胞系（H-1 R）。3-（3，4-二甲基-噻唑-2-基）2，5-二苯基四氮唑溴化物（MTT）测定表明H-1 R对CDDP的抗性比H-1高10倍。当我们使用内部cDNA微阵列比较细胞系中的基因表达水平时，其中代表了来自正常口腔组织、原发性口腔癌和口腔癌细胞系的2，201个基因，确定了12个基因，其在H-1 R中的mRNA表达高于H-1。其中，通过半定量逆转录-聚合酶链反应（PCR）或实时PCR进一步证实了ATP结合盒转运体基因（MDR 1、MRP 1和MRP 2）、CD 55和PGK 1的表达上调以及Caveolin 1的表达下调。我们的研究结果表明，H-1和H-1 R细胞系可能有助于阐明负责CDDP抗性的候选基因，包括本研究中发现的基因。
Cisplatin (CDDP) is a widely used potent chemotherapeutic agent for many malignancies. However, the mechanism of resistance to CDDP remains unclear. To investigate the molecular mechanism, we established a CDDP-resistant cell line (H-1R) from a CDDP-sensitive cell line (H-1) which was derived from moderately differentiated squamous cell carcinoma of the lower gingiva. The 3-(3,4-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay indicated that H-1R had a 10-fold greater resistance to CDDP than H-1. When we compared gene expression levels in the cell lines using an in-house cDNA microarray, which represented 2,201 genes originating from normal oral tissue, primary oral cancer, and oral cancer cell lines, 12 genes showing elevated mRNA expression in H-1R compared with H-1 were identified. Among them, the up-regulated expression of ATP-binding cassette transporter genes (MDR1, MRP1, and MRP2), CD55, and PGK1 and down-regulated expression of Caveolin 1 were further confirmed by semiquantitative reverse transcriptase-polymerase chain reaction (PCR) or real-time PCR. Our results suggest that H-1 and H-1R cell lines could be useful for elucidating the candidate genes responsible for CDDP resistance, including the genes found in this study.