Coussons_2012.pdf (150.05 kB)
Pharmacological Isolation of Experimental Models of Drug-resistant Hepatocellular Carcinoma Cell Line
journal contribution
posted on 2023-07-26, 14:10 authored by Benedict O. Odii, Peter J. CoussonsDrug resistance is one of the major challenges facing the success of chemotherapy against human hepatocarcinoma (HCC) as well as other types of cancer. Studies with cell lines can serve as initial screening for agents that could modulate drug resistance. Development of a good experimental model of drug-resistant cells is a prerequisite for the success of such cellular studies; but could be laborious and generally time-consuming. Additionally, the high mortality rate associated with advanced HCC calls for a probe into the mechanism of resistance by developing experimental model that mimics clinical method of its treatment. Consequently, we have reported a simplified method of selection of drug-resistant hepatocarcinoma cells from human hepatocellular carcinoma (HEPG2) cell line using pharmacologic agents, cisplatin (CDDP) and 5-fluorouracil (5-FU). HEPG2 cell line was incubated for 24 hours with different concentrations of CDDP (0 - 20 μM) or 5-FU (0 - 100 μM). Cell viability was assayed by CCK-8 (Cell Counting Kit) analysis, and the inhibitory concentrations (IC50) for CDDP and 5-FU were established by dose-dependent cytotoxicity curves. The IC50(s) were confirmed by flow cytometric analysis of cell death due to CDDP or 5-FU. Clinical method of treatment was imitated by treating the parental HEPG2 cell line in pulse, at the optimal concentration of either CDDP or 5-FU for 4 to 6 hours. Induction was repeated 6 times, whilst allowing the cells to attain at least 70% confluence between intervals of induction. The resultant drug-resistant sublines, (HEPG2CR) and (HEPG2FR) were found to be stable after over 3 months of drug withdrawal and maintenance in drug-free medium. This was done with the views of establishing a simple, efficient and direct protocol for the development of good cellular models for the study of drug resistance in liver cancer, with possible application in other cancer types.
History
Refereed
- Yes
Volume
3Issue number
4Page range
216-221Publication title
Journal of Cancer TherapyISSN
2151-1942External DOI
Publisher
Scientific Research PublishingFile version
- Published version
Language
- eng
Official URL
Legacy posted date
2017-09-21Legacy creation date
2017-09-21Legacy Faculty/School/Department
ARCHIVED Faculty of Science & Technology (until September 2018)Usage metrics
Categories
No categories selectedLicence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC