Reversal effect of Dioscin on multidrug resistance in human hepatoma HepG2/adriamycin cells |
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Authors: | Sun Bu Tong Zheng Li Hua Bao Yong Li Yu Chun Lei Wu Yin Meng Xiang Ying Li Yu Xin |
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Affiliation: | aNational Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, 130024, ChangChun, China;bResearch Center of Agriculture and Medicine Gene Engineering of Ministry of Education, Northeast Normal University, 130024, ChangChun, China;cInstitute of Genetics and Cytology, Northeast Normal University, 130024, ChangChun, China |
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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 2 kb 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. |
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Keywords: | Multidrug resistance P-glycoprotein Dioscin |
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