Clusterin confers paclitaxel resistance in cervical cancer

Gynecol Oncol. 2006 Dec;103(3):996-1000. doi: 10.1016/j.ygyno.2006.06.037. Epub 2006 Aug 4.

Abstract

Objective: To measure clusterin expression in cervical cancer tissues and cell lines and to evaluate whether clusterin confers resistance to paclitaxel in cervical cancer cells.

Methods: Immunohistochemical staining for clusterin was performed on 15 normal cervical tissues and 32 primary cervical cancer tissues, and clusterin expression in cervical cancer cell lines was quantified by Western blotting. The correlation between clusterin expression level and paclitaxel IC50 in cervical cancer cell lines was evaluated. The effect of clusterin siRNA on paclitaxel resistance was evaluated by XTT assays.

Results: Cervical cancer tissues expressed significantly higher levels of clusterin than did normal cervical tissues (4.08 vs. 1.35, P<0.05). Clusterin expression levels were correlated with paclitaxel resistance in cervical cancer cell lines, and transfection of clusterin siRNA into HeLaS3 cells significantly decreased their resistance to paclitaxel (P<0.05).

Conclusion: Our finding that clusterin expression was significantly higher in cervical cancer than in normal cervical tissues suggests that clusterin may confer paclitaxel resistance in cervical cancer cells.

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Case-Control Studies
  • Cell Line, Tumor / drug effects
  • Clusterin / metabolism*
  • Drug Resistance, Neoplasm*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Inhibitory Concentration 50
  • Middle Aged
  • Paclitaxel / pharmacology*
  • Paclitaxel / therapeutic use
  • Polymerase Chain Reaction
  • RNA, Small Interfering / analysis
  • Uterine Cervical Neoplasms / drug therapy
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology

Substances

  • Antineoplastic Agents, Phytogenic
  • Clusterin
  • RNA, Small Interfering
  • Paclitaxel