PDF(Pubmed)
Abstract：
UNASSIGNED: Triple-negative breast cancer (TNBC) is a very aggressive subset of breast cancer, with limited treatment options, due to the lack of three commonly targeted receptors, which merits the need for novel treatments for TNBC. Towards this need, the use of metformin (Met), the most widely used type-2 diabetes drug worldwide, was explored as a repurposed anticancer agent. Cancer being a metabolic disease, the modulation of two crucial metabolites, glucose, and reactive oxygen species (ROS), is studied in MDA-MB-231 TNBC cells, using Met in the presence of electrical pulses (EP) to enhance the drug efficacy.
UNASSIGNED: MDA-MB-231, human TNBC cells were treated with Met in the presence of EP, with various concentrations Met of 1 mmol/L, 2.5 mmol/L, 5 mmol/L, and 10 mmol/L. EP of 500 V/cm, 800 V/cm, and 1,000 V/cm (with a pulse width of 100 µs at 1 s intervals) were applied to TNBC and the impact of these two treatments was studied. Various assays, including cell viability, microscopic inspection, glucose, ROS, and wound healing assay, were performed to characterize the response of the cells to the combination treatment.
UNASSIGNED: Combining 1,000 V/cm with 5 mmol/L Met yielded cell viability as low as 42.6% at 24 h. The glucose level was reduced by 5.60-fold and the ROS levels were increased by 9.56-fold compared to the control, leading to apoptotic cell death.
UNASSIGNED: The results indicate the enhanced anticancer effect of Met in the presence of electric pulses. The cell growth is inhibited by suppressing glucose levels and elevated ROS. This shows a synergistic interplay between electroporation, Met, glucose, and ROS metabolic alterations. The results show promises for combinational therapy in TNBC patients.
UNASSIGNED: MDA-MB-231, human TNBC cells were treated with Met in the presence of EP, with various concentrations Met of 1 mmol/L, 2.5 mmol/L, 5 mmol/L, and 10 mmol/L. EP of 500 V/cm, 800 V/cm, and 1,000 V/cm (with a pulse width of 100 µs at 1 s intervals) were applied to TNBC and the impact of these two treatments was studied. Various assays, including cell viability, microscopic inspection, glucose, ROS, and wound healing assay, were performed to characterize the response of the cells to the combination treatment.
UNASSIGNED: Combining 1,000 V/cm with 5 mmol/L Met yielded cell viability as low as 42.6% at 24 h. The glucose level was reduced by 5.60-fold and the ROS levels were increased by 9.56-fold compared to the control, leading to apoptotic cell death.
UNASSIGNED: The results indicate the enhanced anticancer effect of Met in the presence of electric pulses. The cell growth is inhibited by suppressing glucose levels and elevated ROS. This shows a synergistic interplay between electroporation, Met, glucose, and ROS metabolic alterations. The results show promises for combinational therapy in TNBC patients.
摘要：
■三阴性乳腺癌（TNBC）是一种非常侵袭性的乳腺癌子集，治疗选择有限，由于缺乏三种常见的靶向受体，这值得对TNBC的新治疗方法的需要。为了这个需要，二甲双胍（Met）的使用，全球使用最广泛的2型糖尿病药物，被探索作为一种再利用的抗癌剂。癌症是一种代谢疾病，两种关键代谢物的调节，葡萄糖，和活性氧（ROS），在MDA-MB-231TNBC细胞中进行了研究，在存在电脉冲(EP)的情况下使用Met增强药物功效。
■MDA-MB-231，人TNBC细胞在EP存在下用Met处理，各种浓度Met为1mmol/L，2.5mmol/L,5mmol/L,和10mmol/LEP为500V/cm，800V/cm,和1,000V/cm（以1s间隔100µs的脉冲宽度）被应用于TNBC，并研究了这两种处理的影响。各种化验，包括细胞活力，显微镜检查,葡萄糖，ROS,和伤口愈合试验，进行以表征细胞对组合处理的响应。
■将1,000V/cm与5mmol/LMet组合在24小时时可产生低至42.6％的细胞活力。与对照组相比，葡萄糖水平降低了5.60倍，ROS水平增加了9.56倍，导致细胞凋亡。
■结果表明，在电脉冲存在下，Met的抗癌作用增强。通过抑制葡萄糖水平和升高的ROS来抑制细胞生长。这表明电穿孔之间的协同相互作用，Met,葡萄糖，和ROS代谢改变。结果显示了在TNBC患者中组合治疗的希望。
■MDA-MB-231，人TNBC细胞在EP存在下用Met处理，各种浓度Met为1mmol/L，2.5mmol/L,5mmol/L,和10mmol/LEP为500V/cm，800V/cm,和1,000V/cm（以1s间隔100µs的脉冲宽度）被应用于TNBC，并研究了这两种处理的影响。各种化验，包括细胞活力，显微镜检查,葡萄糖，ROS,和伤口愈合试验，进行以表征细胞对组合处理的响应。
■将1,000V/cm与5mmol/LMet组合在24小时时可产生低至42.6％的细胞活力。与对照组相比，葡萄糖水平降低了5.60倍，ROS水平增加了9.56倍，导致细胞凋亡。
■结果表明，在电脉冲存在下，Met的抗癌作用增强。通过抑制葡萄糖水平和升高的ROS来抑制细胞生长。这表明电穿孔之间的协同相互作用，Met,葡萄糖，和ROS代谢改变。结果显示了在TNBC患者中组合治疗的希望。
