Predicting the chemosensitivity of pancreatic cancer cells by quantifying the expression levels of genes associated with the metabolism of gemcitabine and 5-fluorouracil
Predicting the chemosensitivity of pancreatic cancer cells by quantifying the expression levels of genes associated with the metabolism of gemcitabine and 5-fluorouracil
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DOI：
10.3892/ijo.2011.1058
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发表时间：
2011-08-01
影响因子：
5.2
通讯作者：
Tanaka, Masao
中科院分区：
文献类型：
--
作者：
Kurata, Nobuaki;Fujta, Hayato;Tanaka, Masao
吉西他滨 (GEM) 是晚期/转移性胰腺癌的标准治疗方法。然而，对于相当一部分患者，GEM 作为单一药物使用时的疗效并不充分。最近，5-氟尿嘧啶 (5-FU) 前药卡培他滨和 S-1 已被单独或与 GEM 组合用作替代品。本研究的目的是研究使胰腺癌细胞对 GEM 和 5-FU 敏感的基因表达模式，并确定个体化化疗的标志物，即使是在已经产生耐药性的患者中也是如此。我们研究了 15 种人类胰腺癌细胞系中与 GEM 和 5-FU 代谢相关的基因表达以及对这些药物的敏感性之间的相关性。我们还建立了 GEM 和 5-FU 耐药性胰腺癌细胞系，以研究这些基因表达水平的变化以及一种药物对另一种药物耐药细胞的影响。我们发现胰腺癌细胞对 GEM- 或 5-FU 的敏感性之间没有相关性。 GEM 抗性细胞不会对 5-FU 产生抗性，反之亦然。 RRMI (P=0.048) 和 TS x DPD (P=0.035) 的高表达分别与 GEM 和 5-FU 的敏感性显着相关。 5-FU 耐药细胞表达的 TP 水平显着高于亲本细胞 (P < 0.05)。总之，胰腺癌细胞对 GEM 和 5-FU 没有表现出交叉耐药性。胰腺癌细胞中 RRMI、TP、DPD 和 TS mRNA 水平的定量分析可能有助于预测其对 GEM 和 5-FU 的敏感性。
Gemcitabine (GEM) is the standard treatment for advanced/metastatic pancreatic cancer. However, there is a substantial subset of patients in whom the efficacy of GEM, when used as a single agent, is inadequate. Recently, the 5-fluorouracil (5-FU) prodrugs capecitabine and S-1 have been used as an alternative, either alone or in combination with GEM. The aim of the present study was to investigate the expression pattern of genes that render pancreatic cancer cells sensitive to GEM and 5-FU, and to identify markers for individualized chemotherapy, even in patients who have developed resistance. We investigated the correlation between the expression of genes associated with the metabolism of GEM and 5-FU, and sensitivity to these drugs in 15 human pancreatic cancer cell lines. We also established GEM- and 5-FU-resistant pancreatic cancer cell lines to investigate changes in the expression levels of these genes and the effects of one drug on cells resistant to the other. We found no correlation between pancreatic cancer cell sensitivity to either GEM- or 5-FU. GEM-resistant cells did not become resistant to 5-FU and vice versa. High expression of RRMI (P=0.048) and TS x DPD (P=0.035) correlated significantly with sensitivity to GEM and 5-FU, respectively. 5-FU-resistant cells expressed significantly higher levels of TP than parental cells (P < 0.05). In conclusion, pancreatic cancer cells showed no cross-resistance to GEM and 5-FU. Quantitative analyses of RRMI, TP, DPD and TS mRNA levels in pancreatic cancer cells may be useful for predicting their sensitivity to GEM and 5-FU.