Pleiotropic-resistant phenotype is a multifactorial phenomenon in human colon carcinoma cell lines

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.