PT  - JOURNAL ARTICLE
AU  - Kwiecińska, Patrycja
AU  - Taubøll, Erik
AU  - Grzyb, Edyta
AU  - Fiedor, Elżbieta
AU  - Ptak, Anna
AU  - Gregoraszczuk, Ewa Lucja
TI  - Valproic Acid as a Promising Co-Treatment With Paclitaxel and Doxorubicin in Different Ovarian Carcinoma Cell Lines
AID  - 10.1097/IGC.0000000000000814
DP  - 2016 Nov 01
TA  - International Journal of Gynecologic Cancer
PG  - 1546--1556
VI  - 26
IP  - 9
4099  - http://ijgc.bmj.com/content/26/9/1546.short
4100  - http://ijgc.bmj.com/content/26/9/1546.full
SO  - Int J Gynecol Cancer2016 Nov 01; 26
AB  - Objective The current preferred treatment of ovarian cancer is combination chemotherapy, usually a platinum-based drug coupled with paclitaxel (PTX). Here, we investigated whether co-treatment with valproic acid (VPA) could increase the efficiency of various ovarian cancer drugs—PTX, doxorubicin (DOX), carboplatin (CBP), and cyclophosphamide (CP)—in different ovarian cancer cell lines.Methods Three different ovarian cancer cell lines (OVCAR-3, TOV-21G, and TOV-112D) were treated with chemotherapeutic drugs, alone or in combination with VPA. Cell viability (XTT assay), caspase-3 activity, and the expression of cell cycle– and apoptosis-related genes and proteins were assessed. Furthermore, the effects of these drugs on α-tubulin acetylation and DNA fragmentation were investigated.Results Paclitaxel and DOX decreased cell viability and increased caspase-3 activity, and co-treatment with VPA enhanced this effect. Carboplatin and CP had no effect. Responses to treatment with PAX and DOX together with VPA on gene expression profile were highly variable and depended on the cell line investigated. However, a common feature in all cell lines was an increased expression of CDKN1A, CCNE1, PARP1, and PARP3. Co-treatment with VPA enhanced the effect of DOX and PAX on most protein expressions investigated in TOV-21G and TOV-112D cell lines, whereas in OVCAR-3, the most effect was seen with DOX with VPA. Valproic acid did not increase PTX-induced α-tubulin acetylation. An additive effect of DOX with VPA on DNA fragmentation was observed in TOV-21G and TOV-112D cell lines but not in the OVCAR-3.Conclusions Our results indicate that VPA could be a promising agent in combined anticancer therapy for ovarian cancer, with the combination of VPA and DOX being the most effective. Certainly, additional in vivo and ex vivo experiments are necessary to investigate the molecular mechanisms of action underlying the cellular effects reported here and to study possible clinically relevant effects in ovarian cancer explants.