Establishment of human pancreatic cancer gemcitabine‑resistant cell line with ribonucleotide reductase overexpression.
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.
Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China.
Congfei
C
Wang
Department of Pharmacology, Fujian Medical University, Fuzhou, Fujian 350004, P.R. China.
Weiwei
W
Zhang
Department of Pharmacology, Fujian Medical University, Fuzhou, Fujian 350004, P.R. China.
Mingjuan
M
Fu
Department of Pharmacology, Fujian Medical University, Fuzhou, Fujian 350004, P.R. China.
Aiqin
A
Yang
Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China.
Heguang
H
Huang
Department of Pharmacology, Fujian Medical University, Fuzhou, Fujian 350004, P.R. China.
Jieming
J
Xie
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects / Q000648:ultrastructure; D002945:Cisplatin / Q000494:pharmacology; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005472:Fluorouracil / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012262:Ribonucleoside Diphosphate Reductase / Q000378:metabolism; D012264:Ribonucleotide Reductases / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D025521:Tumor Suppressor Proteins; D003841:Deoxycytidine; D012264:Ribonucleotide Reductases; C093713:ribonucleotide reductase M2; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; D002945:Cisplatin; D005472:Fluorouracil; D000093542:Gemcitabine