Enhanced chemotherapeutic efficacy of docetaxel in human lung cancer cell line via GLUT1 inhibitor

by Selleckchem | Aug 03 2023

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.

Comments:

The research described aims to investigate the potential benefits of combining a GLUT1 inhibitor with the anticancer agent docetaxel in the treatment of lung cancer. GLUT1 is a protein involved in glucose uptake by cells, including cancer cells, which often exhibit high glucose consumption. The objective of the study is to assess whether inhibiting GLUT1 can enhance the effectiveness of docetaxel by reducing glucose consumption in cancer cells, leading to increased cytotoxicity and apoptosis.

The researchers employed several methods to evaluate the effects of the combined treatment. Cell cytotoxicity was assessed using the methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, which measures the viability of cells. Annexin V/PI double staining was used to determine the percentage of apoptotic cells, providing insights into the induction of programmed cell death. Quantitative real-time polymerase chain reaction (RT-PCR) analysis was conducted to examine the expression levels of genes involved in the apoptosis pathway, specifically Bcl-2, Bax, and Ki-67.

The IC50 values for docetaxel and the GLUT1 inhibitor (BAY-876) were determined as 3.7 ± 0.81 nM and 34.1 ± 3.4 nM, respectively. The severity of the combined effects of these agents on each other was calculated using the synergy finder application. The results indicated that the percentage of apoptotic cells significantly increased to 48.1 ± 2.8% when docetaxel and BAY-876 were co-administered. Furthermore, compared to treatment with docetaxel alone, the combination therapy resulted in a significant decrease in the transcript levels of the anti-apoptotic protein Bcl-2 and the proliferation marker Ki-67, as well as a notable increase in the level of the pro-apoptotic protein Bax (p < 0.05).

The researchers utilized the synergy finder highest single agent (HSA) method to quantify the synergistic effect of the combined treatment. The HSA synergy score was calculated as 28.055, indicating a strong synergistic interaction between BAY-876 and docetaxel.

Based on these findings, the study suggests that the combination of a GLUT1 inhibitor and docetaxel holds promise as a therapeutic approach for lung cancer patients. By targeting glucose consumption and enhancing apoptosis, this combined treatment strategy may provide improved efficacy compared to docetaxel alone. However, it is important to note that this research represents a specific study, and further investigations and clinical trials are necessary to validate the potential clinical benefits of this approach.