PURPOSE ABCC11/MRP8 (ABCC11) is an ATP-binding cassette transporter that is involved in regulating cellular sensitivity and resistance for many anti-cancer drugs. Since 5-fluorouracil (5-FU) is one of the substrates for ABCC11, we examined whether ABCC11 is a predictive marker for an oral 5-FU derivative drug S-1 treatment in non-small cell lung cancer (NSCLC). METHODS Real-time PCR and MTS assay were carried on 21 human NSCLC cell lines. The drug resistance capabilities of ABCC11 are evaluated by analyzing the resistance profiles of a clone of HeLa cell in which the pump was ectopically expressed. Blood samples of 106 NSCLC patients were collected. RESULTS There was a significant correlation between dihydropyrimidine dehydrogenase (DPD) gene expression and the IC50 for 5-FU. We then classified NSCLC cell lines into two groups based on the phenotype of the SNP538 (G > A) in ABCC11: a combined G/G and G/A group, and an A/A group. The distribution of the IC50 for 5-FU in combination with a potent inhibitor of DPD 5-chloro-2, 4-dihydropyrimidine (CDHP), which is contained in S-1, showed a significant reduction in the A/A group compared with the combined G/G and G/A group. Next, the clinical usefulness of the ABCC11 SNP in treatment containing S-1 was examined in 106 NSCLC patients, and the disease control rate was found to be significantly better in the A/A group than in the combined G/G and G/A group. CONCLUSIONS These results indicate that the SNP538(G > A) in the ABCC11 gene is a potential determinant for S-1 treatment.

中文翻译：

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ABCC11基因多态性可作为非小细胞肺癌口服5-氟尿嘧啶衍生物药物S-1治疗的潜在预测生物标志物。

目的ABCC11 / MRP8（ABCC11）是一种ATP结合盒式转运蛋白，参与调节许多抗癌药物的细胞敏感性和耐药性。由于5-氟尿嘧啶（5-FU）是ABCC11的底物之一，因此我们检查了ABCC11是否是非小细胞肺癌（NSCLC）口服5-FU衍生药物S-1治疗的预测指标。方法对21例人NSCLC细胞进行实时PCR和MTS检测。通过分析异位表达泵的HeLa细胞克隆的耐药性，可以评估ABCC11的耐药性。收集了106名NSCLC患者的血液样本。结果二氢嘧啶脱氢酶（DPD）基因表达与5-FU的IC50呈显着相关。然后，我们基于ABCC11中SNP538的表型将NSCLC细胞系分为两组：G / G和G / A组合组和A / A组。与S-1中包含的DPD 5-氯-2、4-二氢嘧啶（CDHP）的有效抑制剂相结合，5-FU的IC50分布与A组相比显着降低。合并的G / G和G / A组。接下来，在106名NSCLC患者中检查了ABCC11 SNP在含S-1的治疗中的临床实用性，发现A / A组的疾病控制率明显优于G / G和G / A合并治疗组。结论这些结果表明，ABCC11基因中的SNP538（G> A）是S-1治疗的潜在决定因素。与S-1中包含的DPD 5-氯-2、4-二氢嘧啶（CDHP）的有效抑制剂相结合，5-FU的IC50分布与A组相比显着降低。合并的G / G和G / A组。接下来，在106名NSCLC患者中检查了ABCC11 SNP在含S-1的治疗中的临床实用性，发现A / A组的疾病控制率明显优于G / G和G / A合并治疗组。结论这些结果表明，ABCC11基因中的SNP538（G> A）是S-1治疗的潜在决定因素。与S-1中包含的DPD 5-氯-2、4-二氢嘧啶（CDHP）的有效抑制剂相结合，5-FU的IC50分布与A组相比显着降低。合并的G / G和G / A组。接下来，在106名NSCLC患者中检查了ABCC11 SNP在含S-1的治疗中的临床实用性，发现A / A组的疾病控制率明显优于G / G和G / A合并治疗组。结论这些结果表明，ABCC11基因中的SNP538（G> A）是S-1治疗的潜在决定因素。在106例NSCLC患者中检查了ABCC11 SNP在含S-1的治疗中的临床实用性，发现A / A组的疾病控制率明显好于G / G和G / A联合治疗组。结论这些结果表明，ABCC11基因中的SNP538（G> A）是S-1治疗的潜在决定因素。在106例NSCLC患者中检查了ABCC11 SNP在含S-1的治疗中的临床实用性，发现A / A组的疾病控制率明显好于G / G和G / A联合治疗组。结论这些结果表明，ABCC11基因中的SNP538（G> A）是S-1治疗的潜在决定因素。