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(As_2O_3)对上述基因表达的影响。方法:采用MTT法检测As_2O_3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:As_2O_3的非细胞毒性剂量为0.2μmol/L,低毒计量为0.8μmol/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。As_2O_3可下调上述基因的表达,而且As_2O_3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,As_2O_3可通过多种机制部分逆转MCF-7/ADM细胞的耐药性。
Objective: To investigate the expression of mdr-1 and mrp genes and observe the effects of arsenic trioxide
(As_2O_3) on the gene expression. Methods: The doze of cytotoxicity and non-cytotoxicity of As_2O_3 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
As_2O_3 was 0. 2μmol/L and the low cytotoxic dose was 0. 8μmol/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 As_2O_3 had more strong effect than the
non-cytotoxic dose of As_2O_3. Conclusions: The strong expressions of mdr-1 and mrp genes were responsible for the in-
duced 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.
出处
《中国肿瘤生物治疗杂志》
CAS
CSCD
2003年第4期285-288,共4页
Chinese Journal of Cancer Biotherapy
基金
辽宁省教委重点资助项目(7907111010)