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Updated: Aug 7, 2026

Deficient Pms2, ERCC1, Ku86, CcOI in Field Defects During Progression to Colon Cancer
Published on: July 29, 2010
Pleiotropic-resistant phenotype is a multifactorial phenomenon in human colon carcinoma cell lines
G Toffoli1, A Viel, L Tumiotto
1Division of Experimental Oncology 1, Centro di Riferimento Oncologico, Aviano, Italy.
Abstract:
The biochemical basis of multidrug-resistant (MDR) phenotype has been investigated in drug-resistant sublines independently obtained in our laboratories by single step doxorubicin (DOX) selection of LoVo, DLD1, and SW948 human colon carcinoma (HCC) cell lines. All the chemoresistant sublines have been found to be cross-resistant to DOX, actinomycin-D (ACT-D) and vincristine (VCR) but not to cis-diamminedichloroplatinum (CDDP), and have exhibited an increased expression level of mdr1 mRNA and gp170 glycoprotein. Comparative analyses in drug-resistant and sensitive cells of resistance index, extracellular and intracellular equitoxic DOX concentrations, and mdr1 gene products expression have indicated that MDR phenotype is a multifactorial phenomenon due to different and possibly independent biochemical mechanisms which cooperate, in varying degrees from cell line to cell line, in conferring cellular chemoresistance.
Insights
Multidrug resistance (MDR) in colon cancer cells involves multiple biochemical mechanisms. These mechanisms confer cross-resistance to certain chemotherapy drugs like doxorubicin but not others.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- The multidrug-resistant (MDR) phenotype is a significant challenge in cancer chemotherapy.
- Understanding the biochemical underpinnings of MDR is crucial for developing effective treatment strategies.
Purpose of the Study:
- To investigate the biochemical basis of the MDR phenotype in human colon carcinoma cell lines.
- To analyze the cross-resistance patterns and molecular alterations in drug-selected sublines.
Main Methods:
- Development of drug-resistant sublines through single-step doxorubicin selection of LoVo, DLD1, and SW948 human colon carcinoma cell lines.
- Assessment of cross-resistance to doxorubicin (DOX), actinomycin-D (ACT-D), vincristine (VCR), and cis-diamminedichloroplatinum (CDDP).
- Quantification of mdr1 mRNA expression and gp170 glycoprotein levels.
Main Results:
- Selected sublines exhibited cross-resistance to DOX, ACT-D, and VCR, but not CDDP.
- Increased expression of mdr1 mRNA and gp170 glycoprotein was observed in chemoresistant sublines.
- Comparative analyses revealed varying degrees of resistance mechanisms across different cell lines.
Conclusions:
- The MDR phenotype in these colon cancer cell lines is a multifactorial phenomenon.
- Cooperating biochemical mechanisms, varying by cell line, contribute to cellular chemoresistance.
- Further research into these mechanisms could inform novel therapeutic approaches for MDR cancers.
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