Gemcitabine induces cell senescence in human pancreatic cancer cell lines.
Patients with pancreatic ductal adenocarcinoma (PDAC) commonly require chemotherapy because they frequently develop metastatic disease or locally advanced tumors. Gemcitabine, an analogue of cytosine arabinoside, is commonly used for PDAC treatment. We observed that gemcitabine induced senescence phenotypes characterized by enhanced senescence-associated β-galactosidase (SA β-Gal) staining and increased expression of senescence-associated molecules in two human pancreatic cancer cell lines, Miapaca-2 and Panc-1, which exhibit resistance to gemcitabine but not L3.pl cells with a high sensitivity to gemcitabine. Gemcitabine-induced cell senescence can be inhibited by reactive oxygen species inhibitor, N-acetyl cysteine. Although gemcitabine also enhanced CXCL8 expression, anti-CXCL8 antibody failed to reduce gemcitabine-induced increases in SA β-Gal-positive cell numbers. These observations would indicate that cell senescence can proceed independently of CXCL8 expression, a characteristic feature of senescence-associated secretion phenotype.
Department of Radiation Oncology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China; Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan.
Yao
Y
Song
Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan.
Tomohisa
T
Baba
Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan. Electronic address: mukaida@staff.kanazawa-u.ac.jp.
Naofumi
N
Mukaida
D016922:Cellular Senescence / Q000187:drug effects*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D010190:Pancreatic Neoplasms / Q000473:pathology*; D000093542:Gemcitabine
D003841:Deoxycytidine; D000093542:Gemcitabine
CXCL8; Gemcitabine; Pancreatic cancer; Senescence