Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.
Cancer Res Treat. 2005 Feb;37(1):54-62. doi: 10.4143/crt.2005.37.1.54. Epub 2005 Feb 28.
Gastric cancer is one of the most prevalent cancers worldwide. 5-fluorouracil (5-FU) and cisplatin are the most commonly used drugs for the treatment of gastric cancer. However, a significant number of tumors often fail to respond to chemotherapy.
To better understand the molecular mechanisms underlying drug resistance in gastric cancer the gene expression in gastric cancer cells, which were either sensitive or resistant to 5-FU and cisplatin, were examined using cDNA microarray analysis. To confirm the differential gene expression, as determined using the microarray, semiquantitative RT-PCR was performed on a subset of differentially expressed cDNAs.
69 and 45 genes, which were either up-regulated (9 and 22 genes) or down-regulated (60 and 25 genes), were identified in 5-FU- and cisplatin-resistant cells, respectively. Several genes, such as adaptor-related protein complex 1 and baculoviral IAP repeat-containing 3, were up-regulated in both drug-resistant cell types. Several genes, such as the ras homolog gene family, tropomyosin, tumor rejection antigen, protein disulfide isomerase-related protein, melanocortin 1 receptor, defensin, cyclophilin B, dual specificity phosphatase 8 and hepatocyte nuclear factor 3, were down-regulated in both drug-resistant cell types.
These findings show that cDNA microarray analysis can be used to obtain gene expression profiles that reflect the effect of anticancer drugs on gastric cancer cells. Such data may lead to the assigning of signature expression profiles of drug-resistant tumors, which may help predict responses to drugs and assist in the design of tailored therapeutic regimens to overcome drug resistance.
胃癌是全球最常见的癌症之一。5-氟尿嘧啶（5-FU）和顺铂是治疗胃癌最常用的药物。然而，相当数量的肿瘤往往对化疗无反应。
为了更好地了解胃癌耐药的分子机制，使用 cDNA 微阵列分析检查了对 5-FU 和顺铂敏感或耐药的胃癌细胞的基因表达。为了确认微阵列确定的差异基因表达，对差异表达 cDNA 的子集进行了半定量 RT-PCR。
在 5-FU 耐药细胞和顺铂耐药细胞中，分别鉴定出 69 个和 45 个基因上调（9 个和 22 个基因）或下调（60 个和 25 个基因）。几种基因，如衔接蛋白相关蛋白复合物 1 和杆状病毒 IAP 重复包含 3，在两种耐药细胞类型中均上调。几种基因，如 ras 同源基因家族、原肌球蛋白、肿瘤排斥抗原、蛋白二硫键异构酶相关蛋白、黑素皮质素 1 受体、防御素、亲环素 B、双特异性磷酸酶 8 和肝细胞核因子 3，在两种耐药细胞类型中均下调。
这些发现表明 cDNA 微阵列分析可用于获得反映抗癌药物对胃癌细胞影响的基因表达谱。这些数据可能导致耐药肿瘤的特征表达谱的分配，这可能有助于预测对药物的反应，并有助于设计克服耐药性的定制治疗方案。
