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China Pharmacy ; (12): 1816-1823, 2020.
Article de Chinois | WPRIM | ID: wpr-823350

RÉSUMÉ

OBJECTIVE:To study the mechanism of Periplaneta americana extract degreasing cream and CⅡ-3(shorted for “degreasing cream ”and“CⅡ-3”)reversing the multi-drug resistance of human HepG 2/ADM cells. METHODS :MTT assay was used to investigate the toxicity effects of different concentrations of sorafenib (positive control ),degreasing cream and C Ⅱ-3 on HepG2/ADM cells ,then IC 20 was calculated. The experiment was divided into sensitivity drug ,drug-resistance group ,sorafenib group,degreasing cream group and C Ⅱ-3 group. HepG 2 cells were included in sensitivity group ,and HepG 2/ADM cells were included in the latter 4 groups. Sensitivity group and drug-resistance group were treated with routine medium ,and other 3 groups were treated with relevant medicine (IC20 as drug concentration ). The content of ADM in HepG 2/ADM cells was determined by Laser scanning confocal microscopy. The expression of apoptosis-related protein as Bcl- 2 and Cleaved-Caspase- 9 p37 were detected by Western blotting assay. RT-qPCR and immunocytochemistry were adopted to detect mRNA and protein expressions that related to multidrug resistance [P-gp (expression produce of MDR1 gene),LRP,BCRP] and that related to enzyme-mediated multidrug resistance pathway (GST-π and Topo Ⅱ). RESULTS :The IC 20 of degreasing cream ,CⅡ-3 and sorafenib were (2.40±0.16), (200.44±27.52),(18.00±1.82)μg/mL,respectively. Compared with sensitivity group ,the protein expressions of Bcl- 2,P-gp, LRP,BCRP and Topo Ⅱ,the mRNA expressions of MDR 1, LRP,BCRP and GST-π were increased significantly in drug resistance group (P<0.05 or P<0.01). Compared with @qq.com drug-resistance group ,the mRNA and protein expression of MDR1 mRNA and LRP ,BCRP,GST-π were significantly decreased in degreasing cream group and C Ⅱ-3 group(P< 0.05 or P<0.01);the protein expression of Bcl- 2 and the mRNA expression of Topo Ⅱ were significantly decreased (P<0.01), while the protein expression level of Cleaved-Caspase- 9 p37 was significantly increased in C Ⅱ -3 group (P<0.05). CONCLUSIONS:Degreasing cream and C Ⅱ-3 can reverse multidrug resistance of HepG 2/ADM cells by reducing drug efflux , promoting cell apoptosis ,reducing the mRNA and protein expression of multi-drug resistance gene as well as gene in enzyme-mediated multi-drug resistance pathway. The effect of C Ⅱ-3 is better than that of degreasing cream.

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