Lee Su Jin, Park Bok-Nam, Roh Jung Hyun, An Young-Sil, Hur Hoon, Yoon Joon-Kee
Department of Nuclear Medicine and Molecular Imaging, Ajou University School of Medicine, Suwon, Republic of Korea.
Department of Surgery, Ajou University School of Medicine, Suwon, Republic of Korea.
Anticancer Res. 2016 Nov;36(11):5975-5980. doi: 10.21873/anticanres.11185.
We assessed the effect of cell-cycle synchronization using the T-type calcium channel inhibitor mibefradil on the anticancer effects of 2-deoxy-D-glucose (2-DG) and glucose metabolism in breast cancer cells.
MDA-MB-231 cells were treated with mibefradil, followed by 2-DG with/without paclitaxel, then cells were assessed for viability. Glucose metabolism was evaluated by H-2-DG uptake, lactate concentration, and membrane glucose transporter 1 expression after mibefradil treatment.
Viability was significantly lower in cells receiving the combination therapy of mibefradil and 2-DG relative to 2-DG treatment alone; addition of paclitaxel to the combination therapy further reduced the viability of breast cancer cells. Withdrawal of mibefradil resulted in a significant increase in cellular H-2-DG uptake uptake, a slight accumulation of lactate, and increased membrane glucose transporter 1 expression.
Mibefradil-induced cell-cycle synchronization enhanced the anticancer activity of 2-DG in breast cancer cells due to an increase in cellular glucose metabolism.
我们评估了使用T型钙通道抑制剂米贝拉地尔进行细胞周期同步化对2-脱氧-D-葡萄糖（2-DG）的抗癌作用及乳腺癌细胞葡萄糖代谢的影响。
用米贝拉地尔处理MDA-MB-231细胞，随后用含或不含紫杉醇的2-DG处理，然后评估细胞活力。在米贝拉地尔处理后，通过H-2-DG摄取、乳酸浓度和膜葡萄糖转运蛋白1表达来评估葡萄糖代谢。
相对于单独使用2-DG治疗，接受米贝拉地尔和2-DG联合治疗的细胞活力显著降低；联合治疗中加入紫杉醇进一步降低了乳腺癌细胞的活力。停用米贝拉地尔导致细胞H-2-DG摄取显著增加、乳酸略有积累以及膜葡萄糖转运蛋白1表达增加。
米贝拉地尔诱导的细胞周期同步化由于细胞葡萄糖代谢增加而增强了2-DG在乳腺癌细胞中的抗癌活性。
