Ciprofloxacin-mediated cell proliferation inhibition and G2/M cell cycle arrest in rat tendon cells

Arthritis Rheum. 2008 Jun;58(6):1657-63. doi: 10.1002/art.23518.


Objective: To investigate the effect of ciprofloxacin on the proliferation and cell cycle progression of tendon cells, and to explore the potential molecular mechanism of ciprofloxacin-associated tendinopathy by analyzing the expression of cell cycle-related cyclin and cyclin-dependent kinase (CDK).

Methods: Rat Achilles tendon cells were treated with ciprofloxacin and then assessed by MTT assay, flow cytometric analysis, and fluorescence confocal microscopy. Levels of messenger RNA (mRNA) for CDK-1 and cyclin B were determined by reverse transcriptase-polymerase chain reaction. Protein expression of CDK-1, cyclin B, checkpoint kinase 1 (CHK-1), and polo-like kinase 1 (PLK-1) was determined by Western blot analysis.

Results: Ciprofloxacin inhibited tendon cell proliferation and caused cell cycle arrest at the G2/M phase. Confocal microscopy revealed that chromosomes in ciprofloxacin-treated cells neither properly aligned along the equatorial planes nor segregated successfully during metaphase. Mitotic arrest, misaligned chromosomes, and poor bipolar spindle formation were observed in ciprofloxacin-treated cells. CDK-1 and cyclin B protein and mRNA were both down-regulated. CHK-1 protein expression was also suppressed, but PLK-1 protein expression was up-regulated by ciprofloxacin.

Conclusion: Our findings suggest a possible mechanism of ciprofloxacin-associated tendinopathy. Down-regulation of CHK-1 and up-regulation of PLK-1 may account for mitotic arrest observed in ciprofloxacin-treated cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Achilles Tendon / cytology*
  • Achilles Tendon / growth & development
  • Animals
  • Cell Cycle / drug effects*
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Ciprofloxacin / pharmacology*
  • Cyclin-Dependent Kinases / drug effects
  • Cyclins / drug effects
  • Nucleic Acid Synthesis Inhibitors / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Tendinopathy / chemically induced
  • Tendinopathy / pathology


  • Cyclins
  • Nucleic Acid Synthesis Inhibitors
  • Ciprofloxacin
  • Cyclin-Dependent Kinases