BACKGROUND: Anaplastic thyroid carcinoma (ATC) is the most aggressive type of thyroid carcinoma. The purpose of this study was to evaluate the combined cytotoxic effects of paclitaxel and lovastatin in ATC cell lines. METHODS: ATC cells were treated with paclitaxel and lovastatin, separately or together, and the cytotoxicity of the compounds was determined by quantifying cell viability and apoptosis. We conducted an isobologram analysis to investigate the combined effect of the two drugs. RESULTS: In 8505C cells, cellular viability was inhibited by lovastatin and paclitaxel in a concentration-dependent manner (p = 0.002 and p = 0.020, respectively). The IC(50) of lovastatin was 3.53 μM and that of paclitaxel was 5.98 nM. In BHT-101 cells, cellular viability was also inhibited in a concentration-dependent manner by lovastatin and paclitaxel (p = 0.020 and p = 0.032, respectively). The IC(50) of lovastatin was 17.13 μM and that of paclitaxel was 35.26 nM. In 8505C cells, paclitaxel and lovastatin alone induced apoptosis in a concentration-dependent manner. However, both an isobologram analysis on inhibition of viability and an analysis of apoptosis demonstrated antagonism between paclitaxel and lovastatin. In BHT-101 cells, however, neither drug had an apoptotic effect when used individually. There was a variable effect when used in combination, depending on the drug concentrations. CONCLUSIONS: Paclitaxel and lovastatin were cytotoxic in two ATC cell lines and increased apoptosis in 8505C cells. However, in these cells, the combination of drugs resulted in antagonism that affected both the cytotoxicity of the compounds and the apoptosis of 8505C cells. The combination of paclitaxel and lovastatin did not enhance the treatment effect in ATC cell lines.
BACKGROUND:Anaplastic thyroid carcinoma (ATC) is the most aggressive type of thyroid carcinoma. The purpose of this study was to evaluate the combined cytotoxic effects of paclitaxel and lovastatin in ATC cell lines. METHODS: ATC cells were treated with paclitaxel and lovastatin, separately or together, and the cytotoxicity of the compounds was determined by quantifying cell viability and apoptosis. We conducted an isobologram analysis to investigate the combined effect of the two drugs. RESULTS: In 8505C cells, cellular viability was inhibited by lovastatin and paclitaxel in a concentration-dependent manner (p = 0.002 and p = 0.020, respectively). The IC(50) of lovastatin was 3.53 μM and that of paclitaxel was 5.98 nM. In BHT-101 cells, cellular viability was also inhibited in a concentration-dependent manner by lovastatin and paclitaxel (p = 0.020 and p = 0.032, respectively). The IC(50) of lovastatin was 17.13 μM and that of paclitaxel was 35.26 nM. In 8505C cells, paclitaxel and lovastatin alone induced apoptosis in a concentration-dependent manner. However, both an isobologram analysis on inhibition of viability and an analysis of apoptosis demonstrated antagonism between paclitaxel and lovastatin. In BHT-101 cells, however, neither drug had an apoptotic effect when used individually. There was a variable effect when used in combination, depending on the drug concentrations. CONCLUSIONS:Paclitaxel and lovastatin were cytotoxic in two ATC cell lines and increased apoptosis in 8505C cells. However, in these cells, the combination of drugs resulted in antagonism that affected both the cytotoxicity of the compounds and the apoptosis of 8505C cells. The combination of paclitaxel and lovastatin did not enhance the treatment effect in ATC cell lines.
Authors: Si Hyoung Kim; Jun Goo Kang; Chul Sik Kim; Sung-Hee Ihm; Moon Gi Choi; Hyung Joon Yoo; Seong Jin Lee Journal: Endocrine Date: 2014-08-06 Impact factor: 3.633