The role of c-myc in regulating mdr1 gene expression in tumor cell line KB

OBJECTIVE: To investigate the relationship between c-myc expression and mdr1 regulation in multidrug resistance (MDR) tumor cell line KBv200. METHODS: A DNA sequence encoding the ribozyme gene was incorporated into a eukaryotic expression vector (pH beta Apr-1 neo) and transfected into the cell line KB, which is resistant to vincristine and expresses the MDR phenotype. The changes of c-myc protein, P-glycoprotein (P-gp) and c-myc mRNA in the KB cell line were assessed before and after treatment with anti-mdr1-ribozyme using immunohisto-chemistry, flow cytometry and semi-quantitative RT-PCR methods. RESULTS: The results demonstrate elevated levels of c-myc mRNA and c-myc protein as well as P-gp in KBv200 cells which are resistant to vincristine (VCR), compared to these of the KB cell which is not resistant to VCR. The expression of c-myc protein, P-gp and c-myc mRNA in the multidrug resistant cell, KBv200, displayed higher than that in the sensitive cell, KB. However, after reversing the multidrug resistance phenotype by anti-mdr1-ribozyme, the level of c-myc protein, P-gp and c-myc mRNA expression showed significant down-regulation in KBv/5 mR3, without difference in KB/5 mR3 and KB. CONCLUSION: The results of our study suggest that there is a close relationship between c-myc gene and mdr1 gene. c-myc may be involved in regulating the expression of mdr1.