通过GLUT1抑制剂增强多西他赛对人类肺癌细胞系的化疗功效。
Enhanced chemotherapeutic efficacy of docetaxel in human lung cancer cell line via GLUT1 inhibitor.
发表日期:2023 Mar 31
作者:
Mona Bahremani, Nadereh Rashtchizadeh, Mehdi Sabzichi, Amir Mansour Vatankhah, Sepideh Danaiyan, Haniyeh Poursistany, Jamal Mohammadian, Amir Ghorbanihaghjo
来源:
GENES & DEVELOPMENT
摘要:
抗癌药剂的剂量依赖性不良反应需要新的方法来减少毒性。当前研究的目标是评估GLUT1抑制剂在增强多西他赛的细胞毒性和细胞凋亡方面的有效性,作为癌细胞中葡萄糖消耗的抑制剂。细胞毒性采用甲基噻唑啉偶氮唑溴化物(MTT)法进行评估。采用Annexin V/PI双重染色法评估细胞凋亡百分比。通过定量实时聚合酶链式反应(RT-PCR)分析检测涉及凋亡通路的基因表达。多西他赛和BAY-876的IC50值分别为3.7±0.81和34.1±3.4 nM。这些药物之间的协同相互作用的严重程度是通过协同发现应用程序计算的。结果显示,在多西他赛和BAY-876联合给药后,凋亡细胞的百分比增加到48.1±2.8%。与没有GLUT1联合给药相比,联合治疗显著降低了Bcl-2和Ki-67的转录组水平,并显著增加了Bax作为促凋亡蛋白的水平(p<0.05)。BAY-876和多西他赛的联合治疗表现出协同作用,这是使用协同发现最高单药(HSA)方法计算的(HSA协同得分:28.055)。这些发现建议将GLUT-1抑制剂和多西他赛的结合治疗作为治疗肺癌患者的一种有前途的疗法。© 2023 Wiley Periodicals LLC.
The dose-dependent adverse effects of anticancer agents need new methods with lesser toxicity. The objective of the current research was to evaluate the efficacy of GLUT1 inhibitor, as an inhibitor of glucose consumption in cancer cells, in augmenting the efficiency of docetaxel with respect to cytotoxicity and apoptosis. Cell cytotoxicity was assessed by using methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. Annexin V/PI double staining was employed to evaluate apoptosis percentage. Quantitative real-time polymerase chain reaction (RT-PCR) analysis was accomplished to detect the expression of genes involved in the apoptosis pathway. The IC50 values for docetaxel and BAY-876 were 3.7 ± 0.81 and 34.1 ± 3.4 nM, respectively. The severity of synergistic mutual effects of these agents on each other was calculated by synergy finder application. It showed that the percentage of apoptotic cells following co-administration of docetaxel and BAY-876 increased to 48.1 ± 2.8%. In comparison without GLUT1 co-administration, the combined therapy decreased significantly the transcriptome levels of the Bcl-2 and Ki-67 and a remarkable increase in the level of the Bax as proapoptotic protein(p < 0.05). Co-treatment of BAY-876 and docetaxel depicted a synergistic effect which was calculated using the synergy finder highest single agent (HSA) method (HSA synergy score: 28.055). These findings recommend that the combination of GLUT-1 inhibitor and docetaxel can be considered as a promising therapeutic approach for the treatment of patients with lung cancer.© 2023 Wiley Periodicals LLC.