Department of Pharmacy, CHU (University Hospital), Dijon, France.
Anticancer Drugs. 2011 Sep;22(8):741-8. doi: 10.1097/CAD.0b013e328346a0c5.
The aim of this study was to select the best candidate drug for transarterial chemoembolization by in-vitro cytotoxic evaluations of 11 anticancer drugs on three human hepatocellular carcinoma (HCC) cell lines. The SNU-398, HepG2, and SNU-449 human HCC cell lines were exposed for 30 min to 11 concentrations of doxorubicin, epirubicin, idarubicin, mitoxantrone, carboplatin, cisplatin, oxaliplatin, 5-fluorouracil, gemcitabine, mitomycin C, or paclitaxel. Cytotoxicity was measured using a quantitative colorimetric assay. For each drug and cell line, we calculated the drug concentration that caused 90% cell death (IC90). To enable comparisons of drugs with different concentration ranges, we computed the cytotoxic index (CyI) as the ratio of maximal drug concentration of more than IC90. Parameters were estimated using nonlinear regression models. Idarubicin was the most active drug on all three cell lines. With SNU-398 cells, the idarubicin CyI was 2.4-fold, 2.5-fold, 57-fold, 148-fold, and more than 58 748-fold higher than the CyIs of mitoxantrone, epirubicin, doxorubicin, gemcitabine, and other drugs, respectively. With HepG2 cells, the idarubicin CyI was 27-fold, 28-fold, 51-fold, and more than 1343-fold higher than the CyIs of doxorubicin, epirubicin, mitoxantrone, and other drugs, respectively. On the resistant SNU-449 cell line, the idarubicin CyI was 2.9-fold and 14-fold higher than the CyIs of paclitaxel and gemcitabine, respectively, the only other drugs effective on this cell line. Among 11 chemotherapeutic agents including doxorubicin, cisplatin, and epirubicin, the most effective on three HCC cell lines was idarubicin. Further clinical investigations are needed to evaluate the safety and efficacy of idarubicin for transarterial chemoembolization in HCC.
本研究旨在通过对三种人肝癌（HCC）细胞系的 11 种抗癌药物的体外细胞毒性评价，选择经动脉化疗栓塞的最佳候选药物。将 SNU-398、HepG2 和 SNU-449 人 HCC 细胞系暴露于 doxorubicin、epirubicin、idarubicin、mitoxantrone、carboplatin、cisplatin、oxaliplatin、5-fluorouracil、gemcitabine、mitomycin C 或 paclitaxel 的 11 种浓度中 30 分钟。使用定量比色法测定细胞毒性。对于每种药物和细胞系，我们计算出导致 90%细胞死亡的药物浓度（IC90）。为了能够比较具有不同浓度范围的药物，我们将细胞毒性指数（CyI）计算为超过 IC90 的最大药物浓度的比值。使用非线性回归模型估计参数。idarubicin 是所有三种细胞系中最有效的药物。对于 SNU-398 细胞，idarubicin 的 CyI 分别比 mitoxantrone、epirubicin、doxorubicin、gemcitabine 和其他药物高 2.4 倍、2.5 倍、57 倍、148 倍和超过 58748 倍。对于 HepG2 细胞，idarubicin 的 CyI 分别比 doxorubicin、epirubicin、mitoxantrone 和其他药物高 27 倍、28 倍、51 倍和超过 1343 倍。在耐药性 SNU-449 细胞系上，idarubicin 的 CyI 分别比 paclitaxel 和 gemcitabine 的 CyI 高 2.9 倍和 14 倍，这是该细胞系上仅有的另外两种有效药物。在包括 doxorubicin、cisplatin 和 epirubicin 在内的 11 种化疗药物中，idarubicin 对三种 HCC 细胞系最有效。需要进一步的临床研究来评估 idarubicin 用于 HCC 经动脉化疗栓塞的安全性和有效性。
