背景：吉西他滨是中晚期胰腺癌的主要化疗药物，但由于胰腺癌对吉西他滨存在高度先天性和获得性耐药，吉西他滨不能明显改善胰腺癌患者的预后。目的：探讨 DNA 损伤修复及其碱基切除修复途径中的关键酶人脱嘌呤/脱嘧啶核酸内切酶1/氧化还原因子-1（APE1/ Ref-1）表达与胰腺癌吉西他滨耐药之间的关系。方法：应用前期研究建立的人胰腺癌吉西他滨耐药细胞株 SW1990-0.5（耐药指数9.32）及其亲本细胞株 SW1990，以彗星实验评估两者经吉西他滨作用后的 DNA 损伤程度，real-time PCR 和蛋白质印迹法检测 APE1/ Ref-1 mRNA 和蛋白表达。结果：经吉西他滨作用24 h，SW1990-0.5和 SW1990细胞的彗星实验 OTM 值分别为0.32±0.13和26.96±6.83，相对于SW1990细胞，SW1990-0.5细胞的 APE1/ Ref-1 mRNA 表达量为2.48±0.49，两者 APE1/ Ref-1蛋白相对表达量分别为1.57±0.08和0.84±0.06，组间差异均有统计学意义（P 均<0.05）。结论：DNA 损伤修复可能与胰腺癌吉西他滨耐药相关，APE1/ Ref-1表达上调可能是通过修复 DNA 损伤参与胰腺癌对吉西他滨耐药。%Background:Gemcitabine is the main drug for chemotherapy of advanced pancreatic cancer,however,the prognosis of pancreatic cancer patients has not been changed obviously because of the high innate and acquired resistance of cancer cells to gemcitabine. Aims:To investigate the correlation of DNA repair and expression of human APE1 / Ref-1(apurinic/apyrimidinic endonuclease 1 / redox factor-1),the key enzyme in base excision repair pathway,with the resistance of pancreatic cancer to gemcitabine. Methods:A gemcitabine-resistant human pancreatic cancer cell line SW1990-0. 5 with a resistance index of 9. 32 and its parental cell line SW1990 were treated with gemcitabine. DNA injury was assessed by comet assay. Expressions of APE1 / Ref-1 mRNA and protein were determined by real-time PCR and Western blotting, respectively. Results:In comet assay,after treated with gemcitabine for 24 hours,OTM value of SW1990-0. 5 and SW1990 cells were 0. 32 ± 0. 13 and 26. 96 ± 6. 83,respectively. Expression level of APE1 / Ref-1 mRNA in SW1990-0. 5 cells was 2. 48 ± 0. 49;and expression levels of APE1 / Ref-1 protein in SW1990-0. 5 and SW1990 cells were 1. 57 ± 0. 08 and 0. 84 ± 0. 06,respectively. Statistically significant differences were existed in all these parameters between SW1990-0. 5 and SW1990 cells(P all < 0. 05). Conclusions:DNA repair might be correlated with the resistance of pancreatic cancer to gemcitabine,and up-regulation of APE1 / Ref-1 might contribute to this resistance by its function on DNA repair.
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