Upregulation of p27Kip1 by demethylation sensitizes cisplatin-resistant human ovarian cancer SKOV3 cells

Mol Med Rep. 2016 Aug;14(2):1659-66. doi: 10.3892/mmr.2016.5399. Epub 2016 Jun 14.


Ovarian cancer has a poor prognosis due to its chemoresistance, and p27Kip1 (p27) has been implicated in tumor prognosis and drug-resistance. However, the regulatory mechanisms of p27 in drug‑resistance in ovarian cancer remain unknown. The current study successfully established chemoresistant cell lines using paclitaxel (TAX), cisplatin (DDP) and carboplatin (CBP) in SKOV3 ovarian cancer cells. The results indicated that the expression levels of p27 were dramatically downregulated in chemoresistant cells. However, 5-aza-2'-deoxycytidine (5-aza) treatment restored p27 expression in DDP-resistant cells, and increased their sensitivity to DDP. In addition, it was observed that the methylation of DDP‑resistant cells, which was downregulated by 5‑aza treatment, was significantly higher compared with SKOV3 cells. Additionally, the overexpression of p27 arrested the cell cycle in S phase and promoted an apoptotic response to DDP. In conclusion, p27 was involved in chemoresistance of SKOV3 cells. Upregulated p27 expression induced by demethylation may enhance sensitivity to DDP through the regulation of the cell cycle.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Azacitidine / analogs & derivatives
  • Azacitidine / pharmacology
  • Cell Cycle / drug effects
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics*
  • DNA Methylation*
  • Decitabine
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Ovarian Neoplasms / genetics*


  • Antineoplastic Agents
  • Cyclin-Dependent Kinase Inhibitor p27
  • Decitabine
  • Azacitidine
  • Cisplatin