Abstract 4549: A comparative efficacy study of Saquinavir in combination with cisplatin or paclitaxel in platinum-resistant ovarian cancer cells

Abstract

Abstract Background and Objective: Ovarian cancer is the 7th most common cancer affecting women Worldwide which has a 5-year survival rate of 45%. First line therapy, platinum and taxol compounds, produces 60% to 80% response rates in platinum sensitive ovarian cancer. However, incidence of resistance to this therapy is high resulting in poor prognosis. The present study evaluated the comparative efficacy of Saquinavir (SAQ) in combination with Cisplatin (CIS) or Paclitaxel (TAX) versus first line therapy, CIS+TAX, in platinum-resistant OVCAR-3 cells. Method: OVCAR-3cells were treated with varying concentrations of SAQ (20μM, 40μM, 60μM and 100μM). OVCAR-3 cells were treated with SAQ (100μM), SAQ+CIS(26μM), SAQ+TAX(1.5nM) and CIS+TAX. Cells were treated over a 24hr period in triplicate. Media only and DMSO only treated cells were used as controls. The cytotoxic effect of each treatment was determined using the automated Trypan Blue exclusion protocol and DNA fragmentation assay was performed to evaluate the mechanisms of induced cell death. Results: Dose dependent and statistically significant (p <0.05) cytotoxic effects were seen with SAQ in OVCAR-3 cells. An IC50 value of 84μM for SAQ was determined in OVCAR-3 cells. Significant cytotoxic effects (p<0.05) in OVCAR-3 treated cells were observed with SAQ, SAQ+TAX, SAQ+CIS AND CIS+TAX combinations when compared to controls. However, SAQ+CIS was the only combination that showed more significant cytotoxicity when compared to CIS+TAX (p = 0.041). SAQ+CIS combination produced an average percentage cell death of 73.25% in OVCAR-3 cells. Cell death by apoptosis was confirmed from observed fragmented DNA in OVCAR-3 cells treated with SAQ+TAX, SAQ+CIS and CIS+TAX. Conclusion: SAQ+CIS produced more significant cytotoxic effect than first line therapy, CIS+TAX, in platinum-resistant ovarian cancer cells. This data supports further evaluation of SAQ for its potential utilization in the treatment of platinum-resistant ovarian cancer. Note: This abstract was not presented at the meeting. Citation Format: Terry-Ann E. Waite, Monique Reboe, Arkene Levy, Sivanesan Dhandayuthapani, Appu Rathinavelu. A comparative efficacy study of Saquinavir in combination with cisplatin or paclitaxel in platinum-resistant ovarian cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4549. doi:10.1158/1538-7445.AM2015-4549