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Assessment of cytotoxicity, apoptosis and DNA damages in Colo320 colorectal cancer cells selected for oxaliplatin resistance
Author(s) -
Virag Piroska,
Brie Ioana,
FischerFodor Eva,
PerdeSchrepler Maria,
Tatomir Corina,
Balacescu Ovidiu,
Irimie Alexandru,
Postescu Ion Dan
Publication year - 2011
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.1754
Subject(s) - oxaliplatin , cytotoxicity , colorectal cancer , apoptosis , cancer research , dna damage , programmed cell death , drug resistance , cancer cell , pharmacology , chemistry , cancer , biology , dna , medicine , in vitro , biochemistry , genetics
Despite the notable efficacy of oxaliplatin in the treatment of colorectal cancers, the metastatic tumours ultimately become resistant to the drug. This study investigated whether the oxaliplatin‐resistant cells display different behaviour to this drug versus the sensitive cells and if this difference may be further exploited into the clinical treatments improvement. In order to establish a stable cell line resistant to oxaliplatin, a human colorectal cancer cell line (Colo320) was exposed to increasing doses of the drug up to the clinically relevant plasma concentration. Four cell groups with different levels of chemoresistance were subjected to additional doses of oxaliplatin, and their cytotoxicity, apoptosis and DNA damage production were assessed. Cells selected for resistance to oxaliplatin reacted differently to the application of additional doses of the drug, displaying lower toxicity and cellular death and fewer DNA cross‐links formation, in accordance with the extent of the oxaliplatin pretreatments. As the cross‐links formation by oxaliplatin being the main cause for cytotoxicity of this drug and a correlation between cytotoxicity and clinical outcome being shown repeatedly, we consider that the evaluation of oxaliplatin‐induced cytotoxicity, apoptosis and DNA damage could be a valuable tool to assess the tumour cells sensitivity and thus to predict the response to chemotherapy. Copyright © 2011 John Wiley & Sons, Ltd.