| Part?: Effect Of Apigenin On The Tumor Multidrug Resistance Cells Growth[Objective] To study the effects of apigenin about cells proliferation,cells cycle distribution and cells apoptosis in the multidrug resistance tumor cells,and to learn the cytotoxicity of apigenin on the tumor multidrug resistance cells.[Methods] The A549/DDP cells and the MCF-7/ADR cells were main objects.The cells those were cultured with different concentrations apigenins(5?mol/L?10?mol/L?20?mol/L?40?mol/L?80?mol/L)were the experimental groups,the cells those were cultured with DDP or ADR were the control groups.Then cells proliferation were detected by MTT methods,cells cycle distribution were detected by PI single stained,cells apoptosis were detected by Annexin V/PI double stained.[Results] There weren't significant difference between the groups that the apigenins concentration were 5?mol/L and 10?mol/L with the control group in cells growth inhibition(P>0.05).There were significant difference between the groups that the apigenin concentration were 20?mol/L,40?mol/L,80?mol/L contrast with the control group cells growth inhibition(P< 0.05).The apigenin delay the A549/DDP cells and MCF-7/ADR cells cycle progress in phase S,there were significant statistical difference between the groups that the apigenin concentration was more than 20?mol/L and the control group(P< 0.05).The apigenin induce apoptosis of A549/DDP cells and MCF-7/ADR cells,and there were significant statistical difference between the groups that the apigenin concentration was more than 20?mol/L and the control group(P < 0.05).Those effection of apigenin on A549/DDP cells and MCF-7/ADR cells were relevant with the apigenin concentration(P < 0.05).[Conclusion]The apigenin inhibited the proliferation of MCF-7/ADR cells and A549/DDP cells,and blocked the cells cycles progress of A549/DDP cells and MCF-7/ADR,and promoted the apoptosis of A549/DDP cells and MCF-7/ADR cells.Part?: Effect Of Apigenin On The Drug Sensitivity And Transport Of The Tumor Multidrug Resistance Cells[Objective] To study the apigenin effects on the drug sensitivity in the tumor multidrug resistance cells and the effects on the drug transport of the tumor multidrug resistance cells,to discuss the role of apigenin in reversing tumor resistance.[Methods] The A549/DDP cells and the MCF-7/ADR cells were the main objects.The apigenin combined with the chemotherapeutic agents for cells were the experimental groups,the chemotherapeutic agents for cells were the control groups.The inhibition rate of A549/DDP cells and MCF-7/ADR cells by the drugs were detected by MTT.And the cells with apigenin in A549/DDP cells and MCF-7/ADR cells were the experimental groups,the cells with chemotherapeutic agents in A549/DDP cells and MCF-7/ADR cells were the control groups,the drug accumulation and efflux in the A549/DDP cells and MCF-7/ADR cells were dected by the Rh-123 retention test.[Results] Among A549/DDP cells,the IC50(DDP)was(14.33±0.41)?g/ml,the IC50(DDP+5?mol/L AP)was(9.81±0.17)?g/ml,the IC50(DDP+10?mol/L AP)was(5.76±0.39),the RI was 1.46 and 2.48 respectively,there were significant statistical difference between the group(DDP+10?mol/L AP)and control group(P < 0.05).Among MCF-7/ADR cells,the IC50(ADR)was(39.83±0.29)?g/ml,the IC50(ADR+5?mol/LAP)was(16.85±0.32)?g/ml,the IC50((ADR+10?mol/LAP)was(12.37±0.58)?g/ml,the RI was 2.36 and3.22 respectively,there were significant statistical difference between the two groups(DDP+5?mol/L AP,DDP+10?mol/L AP)and control group had(P < 0.05).The apigenin made the accumulation of Rh-123 in A549/DDP cells and MCF-7/ADR cells increased,there were statistically significant between the apigenin group and the control group except the 5?mol/L apigenin group(P < 0.05).[Conclusion]The apigenin reverse tumor resistance in A549/DDP cells and MCF-7/ADR cells,and the mechanism relevant increase intracellular drugs accumulation.Part?: Effects Of Apigenin On The Expression Of Multidrug Resistance Proteins And Genes Transcription In The Tumor Multidrug Resistance Cells[Objective]To study the effects of apigenin on the multidrug resistance related proteins expression and the gene transcription level in the tumor multidrug resistance cells,to explore the mechanism about the apigenin reversed tumor multidrug resistance.[Methods]The A549 cells,the A549/DDP cells,the MCF-7 cells,the MCF-7/ADR cells were the main objects.The tumor multidrug resistance cells those were cultured with give different concentration apigenin(5?mol/L?10?mol/L?20?mol/L?40?mol/L?80?mol/L)were experimental groups,those A549/DDP cells and MCF-7/ADR cells without apigenin were the control groups,those A549 cells and MCF-7 cells were negative control groups.The P-gp,MRP,BCRP,LRP expression were detected by Western Blot and the transcription MDR1 m RNA,MRP m RNA,BCRP m RNA,LRP m RNA level were detected by RT-PCR.[Results] The expression of P-gp,MDR1 m RNA,MRP,MRP m RNA,BCRP,BCRP m RNA,LRP,LRP m RNA were low level in A549 cells and MCF-7 cells.The expression of P-gp,MDR1 m RNA,MRP,MRP m RNA,LRP,LRP m RNA were high in A549/DDP cells,the expression of BCRP,BCRP m RNA were lower in A549/DDP cells.The expression of P-gp and MDR1 m RNA in A549/DDP cells were down regulated with the apigenin interfering,and the other proteins expressions and the genes transcription level weren't changed in A549/DDP cells with the apigenin interfering.The expression of P-gp,MDR1 m RNA,MRP,MRP m RNA,BCRP,BCRP m RNA were high level in MCF-7/ADR cells,the expression of LRP,LRP m RNA were lower level in MCF-7/ADR cells.The expression of P-gp and MDR1 m RNA in MCF-7/ADR cells were down regulated with the apigenin interfering,and the other proteins expressions and the genes transcription level weren't changed in MCF-7/ADR cells with the apigenin interfering.[Conclusion] The apigenin down regulated the expression of P-gp and the transcription level of MDR1 m RNA in A549/DDP cells and MCF-7/ADR cells,then reduced the drug resistance mediated by P-gp and reversed the drug resistance of tumor cells. |
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