Investigation of the simultaneous effect of docetaxel and glucose transporter type 1 inhibitor on the expression of apoptotic genes in A549 lung cancer cell line

Abstract

Harmful side effects depending on the dose of anticancer agents have led to the invention of new methods to increase the effectiveness of chemotherapy. The purpose of this research is to estimate the potential of BAY-876 in increasing the efficacy of docetaxel in terms of cytotoxicity, apoptosis and the synergistic effect between the two agents. Methods: Cytotoxicity was evaluated using MTT method. Annexin V/PI double staining was used to check the apoptosis rate. Quantitative real-time PCR analysis was performed to detect the expression of genes involved in the apoptosis pathway. Results: IC50 values for docetaxel and BAY-876 were 3.7 ± 0.81 nM and 34.1 ± 3.4 nM, respectively. The synergistic effect between two agents was calculated using software. Compared to the treatment with single drug, the percentage of apoptotic cells after simultaneous treatment with docetaxel and BAY-876 increased to 48.1 ± 2.8%. Compared to individual treatment, the present study showed a significant decrease in the transcription levels of Bcl-2 and Ki-67 and a significant increase in the level of Bax as a pro-apoptotic protein (P<0.05). The combined treatment of BAY-876 and docetaxel showed a synergistic effect, which was calculated by the HSA algorithm of the SynergyFinder software (synergistic score: HSA 28/055).