Abstract
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 IC50 and IC90 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 (CyI90 = C Max/IC90) 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.
Highlights
IntroductionColorectal cancer (CRC) represents the third most common type of cancer in the world and the second in terms of cancer mortality [1]
No cell line exhibited any major resistance to idarubicin, except at very low concentrations for Caco-2 and SW480
For these 2 cell lines, we observed that 10% of cell viability was achieved after 7 dilutions of idarubicin
Summary
Colorectal cancer (CRC) represents the third most common type of cancer in the world and the second in terms of cancer mortality [1]. Synchronous colorectal liver metastases (CRLM) occur in up to 50% of patients [2]. Complete surgical resection represents the best treatment for long-term survival. Even though less than 25% of patients are initially eligible for liver surgery [3], liver metastases may become resectable after chemotherapy
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