Abstract
Aim:To evaluate the anti-cancer effects of fluoxetine alone or in combination with carboplatin against ovarian carcinoma A2780 cell line.
Methods:
The anticancer effect of fluoxetine on A2780 cell line was assessed through MTT assay, and the results were compared with carboplatin (1nM to 100 µM). Then, the combinational effect of fluoxetine and carboplatin together was investigated. In addition, the effect of cell line recovery therapy was considered and evaluated. After that, cell migration was investigated with or without fluoxetine treatment through the scratch assay.
Results:
The results revealed that both fluoxetine and carboplatin induced cytotoxicity in a dose dependent and time-dependent manner when cells were treated for 48 and 96 h and not 24 h. The IC50s after 48 hours were 42.38±8.11 µM for carboplatin and 43.68±6.31 µM for fluoxetine. While after 96 hours, IC50s of carboplatin and fluoxetine were 7.78±2.26 and 21.15±7.52 µM, respectively. Although the results of single therapy with fluoxetine and carboplatin revealed that 24-hour exposure time is not sufficient to induce required cytotoxicity, however, when the drugs were replaced with fresh media without any drugs and the cells were left for a further 72 h, i.e., following a recovery therapy, cell viability was significantly reduced. The obtained IC50 values for carboplatin and fluoxetine after recovery therapy were 7.74±2.51 and 38.80±4.06 µM, respectively. In separate experiments, a combination of fluoxetine (1 and 10 µM) with carboplatin (1nM to 100 µM), with a 2-hour interval, induced IC50 values of 3.68±0.38 and 3.39±0.25 µM, respectively, after 96 hours. When, pretreatment was performed with fluoxetine 1 and 10 µM, and then carboplatin was added after 4 hours, IC50s were 4.14±0.72 and 5.12±2.50 µM, respectively. Finally, combination therapy with fluoxetine 1 and 10 µM and carboplatin, with a 24-hour interval, resulted in IC50s of 6.63±1.24 and 3.36±1.35 µM, respectively, after 96 hours. The results of the scratch assay revealed that fluoxetine may induce resistance in cell migration when compared with vehicle-treated cells.
Conclusions:
Treatment of the cells with fluoxetine showed promising concentration- and time-dependent cytotoxicity effect against A2780 ovarian cancer cell line. Further experiments using resistant cells are required to substantiate the findings.
| Date of Award | 2 Sept 2026 |
|---|---|
| Original language | English |
| Supervisor | Farideh Javid (Main Supervisor) & Jessica Senior (Co-Supervisor) |