Fohlen Audrey, Bordji Karim, Assenat Eric, Gongora Céline, Bazille Céline, Boulonnais Jérémy, Naveau Mikaël, Breuil Cécile, Pérès Elodie A, Bernaudin Myriam, Guiu Boris
UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, GIP CYCERON, Normandie University, 14000 Caen, France.
Urodigestive Imagery and Interventional Radiology Department, University Hospital of Caen, CEDEX, 14000 Caen, France.
Pharmaceuticals (Basel). 2021 Jul 1;14(7):639. doi: 10.3390/ph14070639.
To treat colorectal liver metastases, intra-arterial chemotherapies may complete therapeutic arsenal. Drugs using intra-arterially are very heterogeneous. The aim of this study was to select the most efficient drug on a panel of colorectal cancer (CRC) cell lines (Caco-2, HCT 116, HT 29, SW 48, SW 480, SW 620) exposed for 30 min to 12 cytotoxic agents (doxorubicin, epirubicin, idarubicin, 5-FU, raltitrexed, gemcitabine, cisplatin, oxaliplatin, mitomycin C, irinotecan, streptozocin, paclitaxel) at different concentrations. The effect on cell viability was measured using the WST-1 cell viability assay. For each drug and cell line, the IC and IC were calculated, which respectively correspond to the drug concentration (mg/mL) required to obtain 50% and 90% of cell death. We also quantified the cytotoxic index (CyI = C Max/IC) to compare drug efficacy. The main findings of this study are that idarubicin emerged as the most cytotoxic agent to most of the tested CRC cell lines (Caco-2, HT29, HCT116, SW620 and SW480). Gemcitabine seemed to be the most efficient chemotherapy for SW48. Interestingly, the most commonly used cytotoxic agents in the systemic and intra-arterial treatment of colorectal liver metastasis (CRLM) (oxaliplatin, 5-FU, irinotecan) showed very limited cytotoxicity to all the cell lines.
为治疗结直肠癌肝转移，动脉内化疗可能完善治疗手段。动脉内使用的药物种类繁多。本研究的目的是在一组结直肠癌（CRC）细胞系（Caco-2、HCT 116、HT 29、SW 48、SW 480、SW 620）中，选择对12种细胞毒性药物（阿霉素、表柔比星、伊达比星、5-氟尿嘧啶、雷替曲塞、吉西他滨、顺铂、奥沙利铂、丝裂霉素C、伊立替康、链脲佐菌素、紫杉醇）在不同浓度下暴露30分钟时最有效的药物。使用WST-1细胞活力测定法测量对细胞活力的影响。对于每种药物和细胞系，计算IC和IC，它们分别对应于导致50%和90%细胞死亡所需的药物浓度（mg/mL）。我们还量化了细胞毒性指数（CyI = C Max/IC）以比较药物疗效。本研究的主要发现是，伊达比星对大多数测试的CRC细胞系（Caco-2、HT29、HCT116、SW620和SW480）而言是细胞毒性最强的药物。吉西他滨似乎是对SW48最有效的化疗药物。有趣的是，在结直肠癌肝转移（CRLM）的全身和动脉内治疗中最常用的细胞毒性药物（奥沙利铂、5-氟尿嘧啶、伊立替康）对所有细胞系的细胞毒性都非常有限。
