Establishment of human pancreatic cancer gemcitabine-resistant cell line with ribonucleotide reductase overexpression

作者：Wang, Congfei; Zhang, Weiwei; Fu, Mingjuan; Yang, Aiqin; Huang, Heguang^*; Xie, Jieming

来源：Oncology Reports, 2015, 33(1): 383-390.

DOI：10.3892/or.2014.3599

• pancreatic cancer
• PANC-1 cell line
• gemcitabine
• resistance
• ribonucleotide reductase

A gemcitabine (GEM)-resistant human pancreatic cancer cell line (PANC-1RG7) was established in vitro by gradually increasing GEM concentrations and cloning cell cultures to develop a cellular model of acquired drug resistance studies. We found that PANC-1RG7 cells exhibited significantly different morphological characteristics from parental cells. PANC-1RG7 cells grew slowly (p<0.05), yet the cell cycle remained unchanged (p>0.05). PANC-1RG7, with a resistance index to GEM of 39.9, showed cross-resistance characteristics to methotrexate, gefitinib, cisplatin and 5-fluorouracil. The proliferation inhibition of GEM was significantly reduced in vivo (p<0.05). The known resistance-associated genes and proteins we detected remained unchanged, with the exception of cytidine deaminase, multidrug resistance-related protein and breast cancer resistance protein genes, which decreased; by contrast, 5-nucleotidase, ribonucleotide reductase (RRM) 1 and RRM2 proteins increased (p<0.05). Therefore, a cell line with acquired GEM resistance was established successfully. Resistance was acquired by overexpressing RRM1 and RRM2 proteins.

• 出版日期2015-1
• 单位福建医科大学