Abstract 16P
Background
Recent years have witnessed a trend to search for the possibility of repurposing widely prescribed drugs in the field of oncology. This applies to thiazolidinediones, peroxisome proliferator-activated receptor-gamma (PPARγ) receptor agonists, the anti-diabetic drugs which showed antitumor activities and evidence for the induction of breast cancer cells differentiation. We aimed to investigate the potential of repurposing a PPARγ ligand, rosiglitazone (RGZ), in combination with either of two chemotherapeutic agents, doxorubicin (Dox) or cisplatin (Cis) for the in vitro treatment of breast cancer cell line, MCF-7.
Methods
The drug combinations were applied to the cells, then viability was measured using MTT assay and trypan blue staining, and Median-effect analysis was performed. The cell cycle was analyzed, and the pattern of cell death was determined using a flow cytometer.
Results
RGZ augmented the growth inhibition effect of Cis and Dox on MCF-7 cells. The synergism was observed only when chemotherapy preceded RGZ and not vice versa, demonstrating a sequence-specific effect. RGZ blocked Dox and Cis cytotoxic outcomes on MCF-7 cells when applied first. The cell cycle and apoptosis/necrosis patterns of cells treated with rosiglitazone followed by the chemotherapy showed similarity to those of cells treated with rosiglitazone alone and suggest that RGZ induced a cell cycle arrest in the G1 phase blocking Dox and Cis subsequent effects.
Conclusions
Combinations of RGZ with Cis showed sequence-specific synergism when RGZ follows chemotherapy unlike the early application of RGZ which blocked the chemotherapy-induced cytotoxicities. We need more experiments to achieve better combinations.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Damascus University.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.