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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >Modulation of multidrug resistance gene expression in human breast cancer cells by (-)-gossypol-enriched cottonseed oil.
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Modulation of multidrug resistance gene expression in human breast cancer cells by (-)-gossypol-enriched cottonseed oil.

机译:富含(-)-棉酚的棉籽油对人乳腺癌细胞中多药耐药基因表达的调节。

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BACKGROUND: Multidrug resistance (MDR) is a major impediment to successful cancer chemotherapy. P-glycoprotein (P-gp), the product of the multidrug resistance 1 (MDR1) gene, acts as an efflux pump and prevents sufficient intracellular accumulation of several anticancer agents, thus, playing a major role in MDR. Tamoxifen (Tam), ICI 182 780 (ICI) and Adriamycin (Adr) alone or with (-)-gossypol-enriched cottonseed oil [(-)-GPCSO] possible effects on cell growth inhibition and regulation of MDR1, mRNA and P-gp expression were examined in both an MDR human breast cancer cell line, MCF-7/Adr cells, and primary cultured human breast cancer epithelial cells (PCHBCEC). MATERIALS AND METHODS: Cells were treated with 0.05% of (-)-GPCSO either in the absence or presence of either 0.1 microM Tam, ICI or Adr for 24 h. RESULTS: Using the non-radioactive cell proliferation MTS assay, none of these chemotherapeutic agents alone inhibited MCF-7/Adr cell and PCHBCEC proliferation; meanwhile, the combination of 0.1 microM Tam, ICI or Adr with 0.05% (-)-GPCSO significantly reduced MCF-7/Adr cell growth by approximately 34%, 32% and 23%, respectively, of that of the vehicle-treated cells. For PCHBCEC, the combination of 0.05% (-)-GPCSO with 0.1 microM of Tam, ICI and Adr reduced cell growth to about 94%, 90%, and 71% respectively, of the vehicle treated PCHBCEC. Furthermore, (-)-GPCSO inhibited MDR1/P-gp expression in both MCF- 7/Adr and PCHBCEC in a dose-dependent manner. Our results provide insight into the MDR-reversing potential of (-)-GPCSO in human breast cancer cells resistant to current chemotherapeutic agents.
机译:背景:多药耐药性(MDR)是成功进行癌症化学疗法的主要障碍。 P-糖蛋白(P-gp)是多药抗性1(MDR1)基因的产物,可作为外排泵并阻止多种抗癌剂在细胞内的充分积累,因此在MDR中起主要作用。他莫昔芬(Tam),ICI 182780(ICI)和阿霉素(Adr)单独或与富含(-)-棉酚的棉籽油[(-)-GPCSO]可能对细胞生长的抑制以及MDR1,mRNA和P-的调节有关在MDR人乳腺癌细胞系MCF-7 / Adr细胞和原代培养的人乳腺癌上皮细胞(PCHBCEC)中都检查了gp表达。材料与方法:在不存在或存在0.1 microM Tam,ICI或Adr的情况下,将细胞用0.05%(-)-GPCSO处理24小时。结果:使用非放射性细胞增殖MTS测定法,这些化学治疗剂均未单独抑制MCF-7 / Adr细胞和PCHBCEC增殖。同时,将0.1 microM Tam,ICI或Adr与0.05%(-)-GPCSO组合使用时,MCF-7 / Adr细胞的生长分别比溶媒处理的细胞分别减少了约34%,32%和23% 。对于PCHBCEC,将0.05%(-)-GPCSO与0.1 microM的Tam,ICI和Adr混合使用,可使细胞生长分别减少至经载体处理的PCHBCEC的约94%,90%和71%。此外,(-)-GPCSO以剂量依赖的方式抑制了MCF-7 / Adr和PCHBCEC中的MDR1 / P-gp表达。我们的结果提供了对(-)-GPCSO在对当前化学治疗剂具有抗性的人乳腺癌细胞中MDR逆转潜力的见解。

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