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Expression of the P-glycoprotein gene in multidrug-resistant Chinese hamster ovary cells
1Department of Molecular Pathology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Abstract:
A series of multidrug-resistant (MDR) Chinese hamster ovary (CHO) cells was established to survive in stepwise increasing concentrations of vincristine. These MDR cells contained amplified P-glycoprotein (mdr) genes. Using monoclonal antibody against the P-glycoprotein, we present here results showing that the levels of P-glycoprotein and its phosphorylation and glycosylation did not correlate with those of drug resistance. Our results suggest that overproduction of the P-glycoprotein cannot account for the differences in drug resistance in these MDR cells, and that multiple modalities are involved in multiple drug resistance in mammalian cells.
Insights
Multidrug resistance (MDR) in Chinese hamster ovary cells is complex. P-glycoprotein levels did not correlate with drug resistance, suggesting multiple factors contribute to MDR.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Multidrug resistance (MDR) is a significant challenge in cancer chemotherapy.
- P-glycoprotein, encoded by mdr genes, is a key transporter implicated in MDR.
- Chinese hamster ovary (CHO) cells are a common model for studying drug resistance mechanisms.
Purpose of the Study:
- To investigate the relationship between P-glycoprotein levels and vincristine resistance in MDR CHO cells.
- To determine if P-glycoprotein overproduction alone explains the observed drug resistance.
- To explore other potential mechanisms contributing to multiple drug resistance in mammalian cells.
Main Methods:
- Establishment of a series of MDR CHO cell lines through stepwise selection in increasing vincristine concentrations.
- Quantification of P-glycoprotein levels using monoclonal antibodies.
- Analysis of P-glycoprotein phosphorylation and glycosylation.
- Correlation analysis between P-glycoprotein characteristics and drug resistance levels.
Main Results:
- MDR CHO cells exhibited amplified mdr genes and increased P-glycoprotein expression.
- The levels of P-glycoprotein, its phosphorylation, and glycosylation did not consistently correlate with the degree of vincristine resistance.
- Significant variations in drug resistance were observed among cell lines with comparable P-glycoprotein levels.
Conclusions:
- P-glycoprotein overproduction is not the sole determinant of multidrug resistance in these MDR CHO cells.
- Multiple cellular mechanisms likely contribute to the observed differences in drug resistance.
- Further research is needed to elucidate the complex interplay of factors involved in mammalian MDR.