Small interfering RNA-mediated silencing of heat shock protein 27 (HSP27) Increases chemosensitivity to paclitaxel by increasing production of reactive oxygen species in human ovarian cancer cells (HO8910)

J Int Med Res. 2009 Sep-Oct;37(5):1375-88. doi: 10.1177/147323000903700512.


Increasing evidence indicates that reactive oxygen species (ROS) are involved in paclitaxel cytotoxicity. Modulating the oxidant-antioxidant status of tumour cells may increase the antitumour activity of paclitaxel. The cytoprotective roles of heat shock protein 27 (HSP27) include chaperoning cellular proteins, regulating apoptotic signalling and modulating oxidative stress. Immunohistochemical staining for HSP27 in human ovarian cancer specimens showed HSP27 was associated with aggressive malignant ovarian disease. Small interfering RNA (siRNA) was used to down-regulate HSP27 in human ovarian cancer cells (HO8910). Reduction of HSP27 expression increased the in vitro chemosensitivity of HO8910 cells to paclitaxel and increased paclitaxel-induced apoptosis and ROS production, although the ROS scavenger, N-acetyl-L-cysteine, partly offset the effects of HSP27 siRNA. Thus, gene knock-down of HSP27 offsets the role of this protein in resisting oxidant stress, thereby indirectly increasing the sensitivity of cells to paclitaxel. The siRNA-induced knock-down of HSP27 could be a novel and potent strategy to help overcome chemotherapeutic resistance to paclitaxel in epithelial ovarian cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Clear Cell / drug therapy
  • Adenocarcinoma, Clear Cell / genetics
  • Adenocarcinoma, Clear Cell / secondary
  • Adenocarcinoma, Mucinous / drug therapy
  • Adenocarcinoma, Mucinous / genetics
  • Adenocarcinoma, Mucinous / secondary
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Blotting, Western
  • Cystadenocarcinoma, Serous / drug therapy
  • Cystadenocarcinoma, Serous / genetics
  • Cystadenocarcinoma, Serous / secondary
  • Drug Resistance, Neoplasm / drug effects*
  • Endometrial Neoplasms / drug therapy
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / secondary
  • Female
  • Gene Silencing
  • HSP27 Heat-Shock Proteins / antagonists & inhibitors
  • HSP27 Heat-Shock Proteins / genetics*
  • HSP27 Heat-Shock Proteins / metabolism
  • Heat-Shock Proteins
  • Humans
  • Immunoenzyme Techniques
  • Molecular Chaperones
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology
  • Paclitaxel / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / pharmacology*
  • Reactive Oxygen Species / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured


  • Antineoplastic Agents, Phytogenic
  • Biomarkers, Tumor
  • HSP27 Heat-Shock Proteins
  • HSPB1 protein, human
  • Heat-Shock Proteins
  • Molecular Chaperones
  • RNA, Messenger
  • RNA, Small Interfering
  • Reactive Oxygen Species
  • Paclitaxel