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Postconfluency MDCK monolayers as an in vitro model of solid tumor chemosensitivity
P Skehan1, J Thomas, S J Friedman
1Department of Pharmacology, Faculty of Medicine, University of Calgary, Alberta, Canada.
Cell Biology and Toxicology
|September 1, 1986
Summary
Canine kidney cells (MDCK) at high density show chemoresistance, similar to solid tumors. This suggests postconfluent monolayers are better models for studying tumor drug sensitivity.
Area of Science:
- Cell Biology
- Pharmacology
- Oncology
Background:
- Canine Madin-Darby kidney (MDCK) cells exhibit slow basal growth post-confluency, with doubling times of 200-300 hours.
- This slow growth rate mirrors that of in vivo solid tumors at clinically relevant sizes.
Purpose of the Study:
- To investigate the chemoresistance of postconfluent MDCK cell monolayers.
- To compare the drug response of high-density cultures with low-density cultures.
Main Methods:
- MDCK cells were cultured to confluency, then treated with deazauridine, deoxyspergualin, and 5-fluorouridine.
- Dose-response curves were generated to assess growth inhibition and cytotoxicity.
Main Results:
- Postconfluent MDCK monolayers showed significant chemoresistance to deazauridine, deoxyspergualin, and 5-fluorouridine compared to sparse cultures.
- Drug concentrations for effective treatment increased by several orders of magnitude in high-density cultures.
- Biphasic dose-response curves indicated potentially different mechanisms for growth inhibition and cytotoxicity.
Conclusions:
- Postconfluent MDCK cell monolayers demonstrate pronounced chemoresistance, analogous to clinical solid tumors.
- These high-density cell cultures may serve as superior in vitro models for evaluating solid tumor chemosensitivity compared to traditional sparse or suspension cultures.