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Reversal effect of Dioscin on multidrug resistance in human hepatoma HepG2/adriamycin cells
Bu Tong Sun1, Li Hua Zheng, Yong Li Bao
1National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, 130024, ChangChun, China.
Abstract:
Multidrug resistance is a serious obstacle encountered in cancer treatment. Since drug resistance in human cancer is mainly associated with overexpression of the multidrug resistance gene 1 (MDR1), the promoter of the human MDR1 gene may be a target for multidrug resistance reversion drug screening. In the present study, HEK293T cells were transfected with pGL3 reporter plasmids containing the 2kb of MDR1 promoter, and the transfected cells were used as models to screen for candidate multidrug resistance inhibitors from over 300 purified naturally occurring compounds extracted from plants and animals. Dioscin was found to have an inhibiting effect on MDR1 promoter activity. The resistant HepG2 cell line (HepG2/adriamycin) was used to validate the activity of multidrug resistance reversal by Dioscin. Results showed that Dioscin could decrease the resistance degree of HepG2/adriamycin cells, and significantly inhibit P-glycoprotein expression, as well as increase the accumulation of adriamycin in HepG2/adriamycin cells as measured by Flow Cytometric analysis. These results suggest that Dioscin is a potent multidrug resistance reversal agent and may be a potential adjunctive agent for tumor chemotherapy.
Insights
Dioscin effectively reverses multidrug resistance in cancer by inhibiting the multidrug resistance gene 1 (MDR1) promoter activity. This natural compound shows potential as an adjunctive therapy to enhance chemotherapy efficacy.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Multidrug resistance (MDR) is a significant challenge in cancer chemotherapy.
- Overexpression of the multidrug resistance gene 1 (MDR1) is a primary cause of MDR in human cancers.
Purpose of the Study:
- To screen for natural compounds that can reverse multidrug resistance.
- To investigate the potential of Dioscin as an MDR reversal agent targeting the MDR1 promoter.
Main Methods:
- HEK293T cells were transfected with MDR1 promoter-luciferase reporter plasmids for drug screening.
- A resistant HepG2/adriamycin cell line was used to validate Dioscin's efficacy.
- Flow cytometry was employed to measure adriamycin accumulation and P-glycoprotein expression.
Main Results:
- Dioscin inhibited MDR1 promoter activity in reporter assays.
- Dioscin decreased the drug resistance of HepG2/adriamycin cells.
- Dioscin significantly reduced P-glycoprotein expression and increased adriamycin accumulation in resistant cells.
Conclusions:
- Dioscin is a potent multidrug resistance reversal agent.
- Dioscin demonstrates potential as an adjunctive therapeutic agent for cancer chemotherapy.
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