Current pharmaceutical design | 2019
Evaluation of cell-detaching effect of EDTA in combination with oxaliplatin for a possible application in HIPEC after cytoreductive surgery: A preliminary in-vitro study.
Abstract
BACKGROUND\nCytoreductive surgery (CRS) combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is an established curative surgical approach in Peritoneal Metastasis (PM). While HIPEC with CRS generally improve survival rates, many patients suffer from PM recurrence even after complete cytoreduction due to residual microscopical tumor cells. Ethylenediaminetetraacetic acid (EDTA), a commonly used compound in laboratory medicine, is known for its membrane-destabilization capacity and cell-detaching effect. This preliminary study aims to assess the potential of EDTA to remove remaining tumor cell clusters when administered during HIPEC.\n\n\nMETHODS\nHT-29 (ATCC® HTB-38™) cells were treated with A) EDTA only B) Oxaliplatin only and C) both agents. Cytotoxicity and cells detachment were measured via colorimetric MTS assay. Additionally, detached cell groups were visualized using light microscopy and further analyzed by means of electron microscopy.\n\n\nRESULTS\nWhen solely applied, EDTA does not exhibit any cell toxicity nor does it add any toxicity to oxaliplatin. However, EDTA enhances the detachment of colon carcinoma adherent cells which corresponds to the level of cell mortality induced by highly concentrated oxaliplatin alone. Detached cells showed no mortality after treatment with EDTA, yet cell clusters showed a decreased amount of extracellular and adhesive matrix in-between cells.\n\n\nCONCLUSIONS\nOur data indicates that EDTA has to potential to remove microscopical tumor cell clusters from the peritoneum and thus act as a supplementary agent in HIPEC procedures. While adding EDTA to HIPEC administrations may significantly decrease the risk of PM recurrences, further in-vivo and clinical trials are required to evaluate this effect.