Resveratrol Enhances Chemosensitivity of AGS Gastric Cancer Cells to Doxorubicin: Focus on Drug Resistance Mechanisms

Abstract

Background: Gastric cancer is one of the common malignancies of the gastrointestinal tract, and chemotherapy with doxorubicin (Dox) is an important therapeutic approach. However, cancer cells develop resistance to Dox over time, reducing the effectiveness of the treatment. Therefore, approaches to improve the chemosensitivity of tumor cells are among the important research goals. Objectives: This study was conducted to investigate the impacts of resveratrol (RSV) on the chemosensitivity of the Dox-treated gastric cancer cell line (AGS). Methods: After preparation and culturing, the AGS cells were treated with RSV and Dox, as well as their combination. Then, cell viability was measured using MTT assays. Finally, the expressions of p53, Bcl-x, MDR1, MRP1, and MRP2 genes were evaluated by RT-PCR after RNA extraction and cDNA synthesis using specific primers. All the data were analyzed using GraphPad Prism software V.8. Results: The RSV was able to exert cytotoxic effects on AGS cells at high concentrations, with its IC50 measured at 50 µg/mL. Importantly, this natural compound was able to improve the chemosensitivity of AGS cells to Dox. Decreased expressions of genes involved in inducing cancer cell resistance to Dox, such as Bcl-x (0.56 ± 0.04 fold change), MDR1 (0.67 ± 0.17 fold change), MRP1 (0.42 ± 0.07 fold change), and MRP2 (0.71 ± 0.08 fold change), were observed in AGS cells treated with RSV+Dox, as measured by RT-PCR. Conclusions: Co-administration of RSV and Dox can improve the chemosensitivity of gastric cancer cells and prevent the development of drug resistance.