Synergistic Cytotoxic Effect of Imiquimod and Cisplatin Combination Therapy on A549 Lung Cancer Cell
Leila Rostamizadeh,1,*Seied Rafi Bahavarnia,2Fatemeh Ramezani,3
1. Department of Molecular Medicine, Faculty of Advanced Medical Science, Tabriz University of Medical Sciences, Tabriz, Iran 2. Screening laboratory, Blood Transfusion Organization, Tabriz, Iran
Introduction: 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: 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: Results: A549 cell viability was affected by single therapy of Cis and IMQ in a dose and timedependent
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: 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.