Document Type : Original Article


1 Division of Medical Biotechnology, Department of Laboratory Sciences, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran

2 Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran

3 School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran


Background: In this study, we aimed to investigate the combined effect of sodium valproate (SV) and lithium (Li) against viability, migration, and invasion of prostate cancer cell line.
Method: In this in vitro study, PC3 cells were treated with different concentrations of SV (2.5, 5.0, and 10 mM) and Li (2.5, 5.0, and 10 µM) either alone or in combination in this in vitro investigation. Using the MTT test and annexin V/7ADD flow-cytometry, cell viability and apoptosis were assessed. Transwell chamber test was used to assess PC3 cells' invasion and migration.
Results: SV and Li alone had no significant on PC3 cell viability. However, the combination of SV and Li in all tested concentrations decreased the viability of PC3 cells in a dose dependent manner (P < 0.001). The combination of SV and Li (5.0 µM + 5.0 mM) increased apoptosis of PC3 cells compared to the control group (P = 0.003). Transwell assay showed that combination of SV with Li (5.0 µM + 5.0 mM) reduced the migration and invasion PC3 cells significantly. The lack of a significant difference between the predicted and observed fractional inhibition for the effects of SV+Li suggests that SV and Li may have synergistic effects on lowering PC3 cell viability and invasiveness.  
Conclusion: This study's findings show that combined low doses of SV and Li could decrease the viability and invasiveness of the PC3 cells; therefore, it can be considered as a new strategy for the treatment of PCa. Furthermore, in vivo studies are required to confirm the results of this study.


This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination, and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi:10.30476/mejc.2022.93057.1676

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