Sequential combination of flavopiridol with Taxol synergistically suppresses human ovarian carcinoma growth.

Abstract

The purpose is to investigate the effects of the sequential combination treatment of Taxol and flavopiridol on human ovarian carcinoma in vitro and in vivo. Cell viabilities were determined using the cell counting kit and by flow cytometry. RT-PCR, TUNEL, and immunoblotting assays were used to detect cellular apoptotic activities following treatments. Tumor growth and microvessel density (MVD) detection of mice bearing SKOV3 cells were studied. Taxol or flavopiridol alone was cytotoxic against SKOV3 cells in vitro with a viability rate of 38.2±1.3% for 1µmol/L Taxol and 44.3±5.9% for 300nM flavopiridol. Sequential combination treatment with Taxol and flavopiridol resulted in a viability rate of 9.1±0.8%. The apoptotic rate of SKOV3 cells was 15.7±1.7, 9.4±0.4 and 51.1±2.5% for Taxol, flavopiridol, and combination of Taxol and flavopiridol, respectively. Significant synergisms were observed in SKOV3 cells in vitro, following the sequential combination of Taxol for 24h followed by flavopiridol for 24h, which resulted in the most substantial cell death and the highest apoptotic rate. All treatments showed significant suppression of tumor growth at the end point of the in vivo study. All treatments significantly reduce the value of MVD. Sequential combination treatment with Taxol and flavopiridol exerted synergistic cytotoxic activities against SKOV3 cells in vitro and significantly suppress the tumor growth of mice bearing SKOV3 cells. It should be further explored as a potential clinically useful regimen against ovarian cancer.