title: Low-dose LBH589 increases the sensitivity of cisplatin to cisplatin-resistant ovarian cancer cells.
abstract: OBJECTIVE
  There is a need to develop alternative therapeutic strategies to overcome cisplatin-associated resistance in patients with ovarian cancer. Histone deacetylation (HDAC) associated with inactivation of genes has been implicated in the epigenetic silencing of tumor suppressor genes affecting critical biological activities in cancer cells and may be an important factor in acquired cisplatin-associated resistance. In this report, we tested a combination of cisplatin and LBH589 (histone deacetylation inhibitor) in cisplatin-resistant ovarian cancer cells to explore the reversal effect of cisplatin resistance and changes of gene expression.
  
  
  METHODS
  To detect the synergistic effects of antiproliferation between cisplatin and LBH589 in ovarian cancer cells, we performed a cell viability assay and a clonogenic assay. To investigate the differences of gene expression between cells treated by cisplatin alone and cotreated with cisplatin and LBH589, a microarray mRNA analysis was performed.
  
  
  RESULTS
  In the presence of low-dose LBH589, the inhibition concentration value of cisplatin for A2780-cp70 cells was much lower than with cisplatin treatment alone. Gene expression profiles identified that a total of 354 genes had been significantly upregulated and a total of 63 genes been downregulated with LBH589 cotreatment.
  
  
  CONCLUSIONS
  We hypothesized that combination of cisplatin and LBH589 can override cisplatin-associated resistance in ovarian cancer cells. These results provide initial evidence for testing this combination in clinical use.
authors.affiliation: Department of Obstetrics and Gynecology, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Yen-Ying
authors.initials: YY
authors.lastname: Ma
authors.forename: Hao
authors.initials: H
authors.lastname: Lin
authors.forename: Jau-Sung
authors.initials: JS
authors.lastname: Moh
authors.forename: Kuang-Den
authors.initials: KD
authors.lastname: Chen
authors.forename: I-Wen
authors.initials: IW
authors.lastname: Wang
authors.forename: Yu-Che
authors.initials: YC
authors.lastname: Ou
authors.forename: Ying-Shu
authors.initials: YS
authors.lastname: You
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Lung
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007211:Indoles; D046228:Microarray Analysis; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000077767:Panobinostat; D012313:RNA / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D006877:Hydroxamic Acids; D007211:Indoles; D012313:RNA; D000077767:Panobinostat; D002945:Cisplatin