Altered stability of etoposide-induced topoisomerase II-DNA complexes in resistant human leukaemia K562 cells
1994

Resistance of K562 Leukaemia Cells to Etoposide

publication 10 minutes Evidence: moderate

Author Information

Author(s): M.K. Ritkel, D. Roberts, W.P. Allan, J. Raymond, V.V. Bergoltz, J.C. Yalowich

Primary Institution: University of Pittsburgh School of Medicine

Hypothesis

Resistance to VP-16 in K562 cells is associated with changes in topoisomerase II.

Conclusion

K/VP.5 cells show reduced topoisomerase II levels and altered drug-induced DNA damage response compared to K562 cells.

Supporting Evidence

  • K/VP.5 cells were 30-fold resistant to VP-16 compared to K562 cells.
  • Topoisomerase II protein levels were reduced 3- to 7-fold in K/VP.5 cells.
  • VP-16-induced DNA damage was less in K/VP.5 cells than in K562 cells.
  • ATP enhanced VP-16-induced DNA damage more in K562 than in K/VP.5 cells.

Takeaway

Some cancer cells can become resistant to a drug called VP-16, and this study found that the reason is changes in a protein that helps manage DNA.

Methodology

K562 leukaemia cells were exposed to etoposide to select for resistant clones, and various assays were performed to measure drug response and topoisomerase II activity.

Limitations

The study primarily focuses on a single cell line and may not generalize to other types of cancer cells.

Statistical Information

P-Value

0.002

Statistical Significance

p<0.05

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