Synergistic Cytotoxic Effect of Imiquimod and Cisplatin Combination Therapy on A549 Lung Cancer Cell

Abstract

Background: Recently, combination therapy has become a promising approach to overcoming chemotherapy problems. In the present study, we describe a combinational treatment regime using cisplatin (Cis) and imiquimod (IMQ) to increase the antitumor response of the therapy in A549 lung cancer cells. Methods: A549 cells were either treated with increasing concentrations of Cis or IMQ or with Cis-IMQ combinations for 24h. Cell growth inhibition, cell cycle analysis, and inductive apoptosis were evaluated using MTT assay and annexin V assay using flow cytometry, respectively. Kruskal-Wallis was used to analyze differences in cell groups’ means. Results: A549 cell viability was affected by single therapy of Cis and IMQ in a dose and time-dependent manner (P<0.001). The combination index (CI) analysis revealed that the combined effect of Cis-IMQ exerted a wide range of synergy in lung cancer cells as well as 0.58 to 0.84 for IC10 to IC90. More interestingly, the combination of Cis and IMQ reduced the dose of Cis by 1.86-fold. In terms of cell apoptosis induction, Cis (IC20)-IMQ (IC90) displayed a synergistic effect on A549 cells, compared to the single drug (P<0.0001). Co-treatment of A549 cells with Cis and IMQ significantly caused SubG1 arrest compared to Single therapy and control group. Conclusion: These results indicated that an IMQ-based combination using Cis has synergistic effects on cell proliferation and apoptosis induction in A549 cells and deserves further preclinical and clinical studies.

Keywords

• synergism
• imiquimod
• cisplatin
• combination therapy
• apoptosis