title: SGI-1776, an imidazo pyridazine compound, inhibits the proliferation of ovarian cancer cells by inactivating Pim-1.
abstract: OBJECTIVE
  To investigate the antitumor effect of SGI-1776 on human ovarian cancer HO-8910 cells and its molecular mechanism.
  
  
  METHODS
  HO-8910 cells were cultured in vitro, and the proliferation inhibitory effects of SGI- 1776 were determined by MTT assay and colony formation assay. The effect of SGI-1776 on the distribution of cell cycle phase was observed by flow cytometry with propidium iodide (PI) staining. The inhibition rate of migration and invasion were valued by transwell cell assay. Multiple molecular techniques, such as ELISA, Western blot, siRNA and cDNA transfection were used to explore the molecular mechanism.
  
  
  RESULTS
  SGI-1776 presented dramatic anti-tumor activity against HO-8910 cells in vitro, inhibited the cells proliferation and colony formation, and attenuated the migration and invasion in a dosedependent manner, accompanied by cell cycle arrest in G1 phase. SGI-1776 caused the proliferation inhibition with concomitant decrease in Pim-1 kinase activity, down-regulated the expression of Pim-1 protein and and its downstream genes, such as CDK6, pCDK6, CDK4, pCDK4, CDK2 and pCDK2, and increased the expression of P21 and P27. Down-regulation expression of Pim-1 by siRNA followed SGI-1776 treatment resulted in enhanced cell proliferation inhibition rate and attenuated migration/invasion. Up-regulation of Pim-1 by cDNA transfection attenuated SGI- 1776-induced cell proliferation inhibition and its migration/invasion.
  
  
  CONCLUSIONS
  Pim-1 mediates the biological effect of SGI-1776 in human ovarian cancer HO-8910 cells, suggesting Pim-1 might be a novel target for human ovarian cancer.
authors: Deparetment of Obstetrics and Gynecology, the First Affiliated Hospital of University of South China, Hengyang Hunan 421001, China.
authors: Jing
authors: J
authors: Xie
authors: Jun
authors: J
authors: Bai
mesh_terms: D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D015536:Down-Regulation; D005260:Female; D018816:Genes, cdc; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D051573:Proto-Oncogene Proteins c-pim-1 / Q000378:metabolism*; D011724:Pyridazines / Q000494:pharmacology*; D034741:RNA, Small Interfering; D015854:Up-Regulation
chemical_list: D007093:Imidazoles; D011724:Pyridazines; D034741:RNA, Small Interfering; C545188:SGI 1776; C496634:PIM1 protein, human; D051573:Proto-Oncogene Proteins c-pim-1