Approximately 1.9 million new cases of colorectal cancer are diagnosed each year [1]. Oxaliplatin (OxaPt) and 5-fluorouracil (5-FU) are the main chemotherapeutics for colorectal cancer, but the development of chemoresistance is almost inevitable. In recent years, it has been established that the incidence of OxaPt and 5-FU resistance can be attributed to the alterations in drug transport, evasion of apoptosis, changes in the cell cycle and DNA-damage repair machinery [2].
One of the ways to study the mechanisms of cancer resistance to chemotherapeutics is by comparing transcriptome and proteome between drug-resistant cancer cell sublines and the parental cell line. In this study, parental human colorectal adenocarcinoma cells DLD-1 were cultured in a medium containing either OxaPt or 5-FU to create sublines that were resistant to each drug. The sublines have the respective names DLD/Oxa and DLD/FU. DLD/Oxa and DLD/FU cells were further characterized by assessing their sensitivity to chemotherapeutic drugs. Cell sensitivity to drug treatment was assayed by two methods, colony forming assay and crystal violet method. Both methods indicated and increased DLD/Oxa cell resistance to OxaPt, but only colony forming assay showed an increased DLD/FU resistance to 5-FU.
Also, to further investigate the drug resistance of the parental and cell sublines mentioned above, combinations of drugs named FOLFOX and FOLFIRI were developed. While 5-FU used as single agent in patients with metastatic colorectal cancer has an objective response rate at a very low percentage, the administration of combinations of irinotecan with 5-FU or OxaPt with 5-FU is speculated to result in increased response rate and improved survival [3]. Cells were treated with drugs according to the standard FOLFOX and FOLFIRI clinical regimens and cell viability was determined with crystal violet staining.
In conclusion, we believe that OxaPt and 5-FU-resistant DLD-1 cell line sublines DLD/Oxa and DLD/FU will be a valuable tool for colorectal cancer studies in the future.