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Updated: Jul 4, 2026
A Three-dimensional Model of Spheroids to Study Colon Cancer Stem Cells
Published on: January 22, 2021
Cellular response to irinotecan in colon cancer cell lines showing differential response to 5-fluorouracil
Kristiane Haug1, K Liza Kravik, Paula M De Angelis
1The Pathology Clinic, Rikshospitalet Medical Center, 0027 Oslo, Norway.
Background:
Use of irinotecan (CPT-11) as second-line therapy for metastatic colorectal cancer has shown some promise in cases where 5-fluorouracil (5-FU) has failed. Cross-resistance to both drugs may however be a potential clinical problem. The cellular response to CPT-11 was investigated in two human colon cancer cell lines that demonstrate a differential response to 5-FU.
Materials And Methods:
Cell cycle progression, clonogenic survival, DNA damage checkpoint activation, apoptosis induction and senescence development were assessed during 48 hours of treatment and 72 hours of recovery.
Results:
Both cell lines had similar cellular response patterns to CPT-11. Growth inhibition, loss of clonogenicity, ataxia telangiectasia mutated (ATM) activation, H2AX phosphorylation, TP53 stabilization, CDKN1A induction, G2/M arrests, endoreduplication, negligible cell death and appearance of a senescence-associated beta-galactosidase phenotype were observed.
Conclusion:
Cross-resistance to 5-FU and CPT-11 was not demonstrated. The appearance of a senescence phenotype in response to CPT-11 treatment may have potential clinical relevance for treatment regimens.
