title: Aspirin inhibits proliferation of gemcitabine-resistant human pancreatic cancer cells and augments gemcitabine-induced cytotoxicity.
abstract: OBJECTIVE
  To investigate whether aspirin is able to augment gemcitabine-induced cytotoxicity in human pancreatic cancer cells.
  
  
  METHODS
  Two gemcitabine-insensitive human pancreatic cancer cell lines, PANC-1 and Capan-1, were used. Cells were treated with either aspirin or gemcitabine alone or both of them. Cell growth and apoptosis were determined by MTT assay, Annexin V or Hoechest 33258 staining. Cell cycle distribution was examined by flow cytometry. Western blot with specific phosphorylated protein antibodies was used to detect the activation of protein kinase. RT-PCR and Western blot were applied to assess the transcription and protein level for cyclin D1 and Bcl-2.
  
  
  RESULTS
  Aspirin alone significantly inhibits the proliferation of PANC-1 cells by causing cell cycle arrest at G(1) phase. Aspirin potentiates the anti-survival effect of gemcitabine as well as its pro-apoptotic effect in PANC-1 cells, although aspirin per se does not trigger apoptosis. Aspirin inhibits GSK-3beta activation and suppresses the expression of its downstream gene products (cyclin D1 and Bcl-2), which are implicated in proliferation, survival and chemoresistance of pancreatic cancer. The effects of aspirin on Capan-1, were similar to that on PANC-1.
  
  
  CONCLUSIONS
  Our results suggest that aspirin inhibits the proliferation of gemcitabine-resistant pancreatic cancer cells and augments the antisurvival effect of gemcitabine, probably by suppressing the activity of GSK-3beta and its downstream gene products.
authors: Department of Pharmacology, Zhong-shan Medical College, Sun Yat-Sen University, Guangzhou, China.
authors: Yan-qiu
authors: YQ
authors: Ou
authors: Wen bo
authors: Wb
authors: Zhu
authors: Yan
authors: Y
authors: Li
authors: Peng-xin
authors: PX
authors: Qiu
authors: Yi-jun
authors: YJ
authors: Huang
authors: Jun
authors: J
authors: Xie
authors: Song-min
authors: SM
authors: He
authors: Xiao-ke
authors: XK
authors: Zheng
authors: Tian-dong
authors: TD
authors: Leng
authors: Dong
authors: D
authors: Xu
authors: Guang-mei
authors: GM
authors: Yan
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001241:Aspirin / Q000494:pharmacology*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000187:drug effects / Q000235:genetics; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004357:Drug Synergism; D005434:Flow Cytometry; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000235:genetics; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D019253:Proto-Oncogene Proteins c-bcl-2; D003841:Deoxycytidine; D019938:Cyclin D1; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D001241:Aspirin; D000093542:Gemcitabine