PDF(Pubmed)
Abstract：
UNASSIGNED: Triple negative breast cancer (TNBC) is usually treated with high doses of paclitaxel, whose effectiveness may be modulated by the action of environmental contaminants such as hexachlorobenzene. High doses of paclitaxel cause adverse effects such as low cellular selectivity and the generation of resistance to treatment due to an increase in the expression of multidrug resistance proteins (MRPs). These effects can be reduced using a metronomic administration scheme with low doses. This study aimed to investigate whether hexachlorobenzene modulates the response of cells to conventional chemotherapy with paclitaxel or metronomic chemotherapy with paclitaxel plus carbachol, as well as to study the participation of the MRP ATP-binding cassette transporter G2 (ABCG2) in human TNBC MDA-MB231 cells.
UNASSIGNED: Cells were treated with hexachlorobenzene alone or in combination with conventional or metronomic chemotherapies. The effects of treatments on cell viability were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and the nuclear factor kappa B pathway participation was evaluated using a selective inhibitor. ABCG2 expression and its modulation were determined by western blot.
UNASSIGNED: Results confirmed that paclitaxel reduces MDA-MB231 cell viability in a concentration-dependent manner. Results also showed that both conventional and metronomic chemotherapies reduced cell viability with similar efficacy. Although hexachlorobenzene did not modify cell viability per se, it did reverse the effect induced by the conventional chemotherapy, without affecting the efficacy of the metronomic chemotherapy. Additionally, a differential modulation of ABCG2 expression was determined, mediated by the nuclear factor kappa B pathway, which was directly related to the modulation of cell sensitivity to another cycle of paclitaxel treatment.
UNASSIGNED: The findings indicate that, in human TNBC MDA-MB231 cells, in the presence of hexachlorobenzene, the metronomic combination of paclitaxel plus carbachol is more effective in affecting the tumor biology than the conventional therapeutic administration scheme of paclitaxel.
UNASSIGNED: Cells were treated with hexachlorobenzene alone or in combination with conventional or metronomic chemotherapies. The effects of treatments on cell viability were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and the nuclear factor kappa B pathway participation was evaluated using a selective inhibitor. ABCG2 expression and its modulation were determined by western blot.
UNASSIGNED: Results confirmed that paclitaxel reduces MDA-MB231 cell viability in a concentration-dependent manner. Results also showed that both conventional and metronomic chemotherapies reduced cell viability with similar efficacy. Although hexachlorobenzene did not modify cell viability per se, it did reverse the effect induced by the conventional chemotherapy, without affecting the efficacy of the metronomic chemotherapy. Additionally, a differential modulation of ABCG2 expression was determined, mediated by the nuclear factor kappa B pathway, which was directly related to the modulation of cell sensitivity to another cycle of paclitaxel treatment.
UNASSIGNED: The findings indicate that, in human TNBC MDA-MB231 cells, in the presence of hexachlorobenzene, the metronomic combination of paclitaxel plus carbachol is more effective in affecting the tumor biology than the conventional therapeutic administration scheme of paclitaxel.
摘要：
■三阴性乳腺癌（TNBC）通常使用高剂量的紫杉醇治疗，其有效性可以通过环境污染物如六氯苯的作用来调节。高剂量的紫杉醇由于多药抗性蛋白(MRP)的表达增加而引起诸如低细胞选择性和对治疗产生抗性的副作用。使用低剂量的节拍给药方案可以减少这些影响。这项研究旨在研究六氯苯是否调节细胞对紫杉醇常规化疗或紫杉醇加卡巴胆碱节拍化疗的反应。以及研究MRPATP结合盒转运蛋白G2（ABCG2）在人TNBCMDA-MB231细胞中的参与。
■用单独的六氯苯或与常规或节拍化学疗法组合处理细胞。通过3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴化物测定法确定处理对细胞活力的影响，并使用选择性抑制剂评估核因子κB途径的参与。通过蛋白质印迹确定ABCG2表达及其调节。
■结果证实紫杉醇以浓度依赖性方式降低MDA-MB231细胞活力。结果还表明，常规和节拍化学疗法均以相似的功效降低了细胞活力。尽管六氯苯本身并没有改变细胞的活力，它确实逆转了传统化疗引起的效果，而不影响节拍化疗的疗效。此外,确定了ABCG2表达的差异调节，由核因子κB途径介导，这与细胞对另一个紫杉醇治疗周期的敏感性的调节直接相关。
■研究结果表明，在人TNBCMDA-MB231细胞中，在六氯苯存在的情况下，紫杉醇与卡巴胆碱的节拍组合比紫杉醇的常规治疗方案更有效地影响肿瘤生物学。
■用单独的六氯苯或与常规或节拍化学疗法组合处理细胞。通过3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴化物测定法确定处理对细胞活力的影响，并使用选择性抑制剂评估核因子κB途径的参与。通过蛋白质印迹确定ABCG2表达及其调节。
■结果证实紫杉醇以浓度依赖性方式降低MDA-MB231细胞活力。结果还表明，常规和节拍化学疗法均以相似的功效降低了细胞活力。尽管六氯苯本身并没有改变细胞的活力，它确实逆转了传统化疗引起的效果，而不影响节拍化疗的疗效。此外,确定了ABCG2表达的差异调节，由核因子κB途径介导，这与细胞对另一个紫杉醇治疗周期的敏感性的调节直接相关。
■研究结果表明，在人TNBCMDA-MB231细胞中，在六氯苯存在的情况下，紫杉醇与卡巴胆碱的节拍组合比紫杉醇的常规治疗方案更有效地影响肿瘤生物学。
