[关键词]
[摘要]
目的: 探讨人乳腺癌阿霉素(ADM)耐药细胞系MCF-7/ADM的mdr-1基因和mrp基因表达,观察三氧化二砷(As2O3)对上述基因表达的影响。方法:采用MTT法检测As2O3的细胞毒性及非细胞毒性剂量,应用RT-PCR检测mdr-1基因和mrp基因的转录表达。结果: As2O3的非细胞毒性剂量为0.2 μmol/L,低毒计量为0.8 μmol/L。Mdr-1基因和mrp基因在MCF-7/ADM细胞中均呈过表达,而且mdr-1的基因表达强于mrp基因,在MCF-7/S细胞中未见表达。As2O3可下调上述基因的表达,而且As2O3低毒剂量的下调作用强于无毒剂量。结论:人乳腺癌MCF-7/ADM细胞获得阿霉素抗药性,与mdr-1基因和mrp基因过表达有关,As2O3可通过多种机制部分逆转MCF7/ADM细胞的耐药性。
[Key word]
[Abstract]
Objective: To investigate the expression of mdr-1 and mrp genes and observe the effects of arsenic trioxide (As2O3) on the gene expression.Methods: The doze of cytotoxicity and non-cytotoxicity of As2O3 was examined through MTT assay. The expressions of mdr-1 and mrp genes were studied by RT-PCR method.Results: The non-cytotoxic dose of As2O3 was 0.2 μmol/L and the low cytotoxic dose was 0.8 μmol/L to MCF-7/ADM cell line(P<0.05). Expression of mdr-1 and mrp genes was positive in MCF-7/ADM cells, and the expression of mdr-1 was stronger than the mrp gene, then the expression of mdr-1 and mrp genes was negative in the MCF-7/S cells; Arsenic trioxide could down-regulate the expression of mdr-1 and mrp genes in MCF-7/ADM and the lowcytotoxic dose of As2O3 had more strong effect than the non-cytotoxic dose of As2O3. Conclusions:The strong expressions of mdr-1 and mrp genes were responsible for the induced resistance of MCF-7/ADM cells to ADM; Arsenic trioxide reverses partly the multidrug resistance of the MCF-7/ADM cells with more kinds of biologic mechanisms.
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[基金项目]
辽宁省教委重点资助项目(7907111010)