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Multidrug resistance increment in a human colon carcinoma cell line by colchicine
M J Ruiz Gómez1, L Gil, A Souviron
1Departamento de Radiología y Medicina Física, Facultad de Medicina, Universidad de Málaga, Spain.
Abstract:
The most important mechanism in drug resistance is the multidrug resistance (MDR) phenomenon. It is possible to select MDR cells by in vitro exposure to cytotoxic agents. The resistance is due to the hyperexpression of the P-glycoprotein (P-Gp) that take drugs out from the cells. In this study, a colchicine resistant subline (HCA-2/1cch) was selected from a human colon adenocarcinoma after a short period of drug exposure, as an in vitro model of drug resistance selection. These cells showed cross-resistance to other drugs, which were not present in the medium during selection. The relative resistance was 3.32 for colchicine, 3.15 for vinblastine, 2.62 for vincristine and 5.22 for mitomycin C. P-glycoprotein levels were assayed by flow cytometry. It was found that a significant increase of 2.35 and 1.59 had occurred in the peak and mean channel of fluorescence, respectively, indicating an increment of P-glycoprotein expression in relation to the parental line. Moreover, verapamil (10 microg/ml) produced a partial reversion of multidrug resistance. The sensitisation rates were 7.41 for colchicine, 1.25 for vinblastine, 2.36 for vincristine and 1.17 for mitomycin C. The data obtained suggest that colchicine exposure period (10 weeks) and dose (0.5 microg/ml) assayed were sufficient to produce an increment in multidrug resistance. This resistance could be due to higher level of P-Gp expression.
Insights
Multidrug resistance (MDR) in cancer cells can be induced by exposing them to cytotoxic agents like colchicine. This study shows that P-glycoprotein (P-Gp) overexpression in colon cancer cells leads to MDR, which can be partially reversed by verapamil.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Multidrug resistance (MDR) is a major challenge in cancer chemotherapy.
- The P-glycoprotein (P-Gp) efflux pump is a key mechanism driving MDR.
- In vitro models are crucial for studying MDR mechanisms and developing reversal strategies.
Purpose of the Study:
- To establish an in vitro model of drug resistance selection using a human colon adenocarcinoma cell line.
- To investigate the role of P-glycoprotein (P-Gp) in colchicine-induced multidrug resistance.
- To evaluate the efficacy of verapamil in reversing multidrug resistance.
Main Methods:
- Selection of a colchicine-resistant subline (HCA-2/1cch) from human colon adenocarcinoma cells.
- Assay of P-glycoprotein (P-Gp) levels using flow cytometry.
- Assessment of drug resistance and verapamil-induced sensitization rates.
Main Results:
- The HCA-2/1cch subline exhibited cross-resistance to colchicine, vinblastine, vincristine, and mitomycin C.
- Significant increases in P-glycoprotein (P-Gp) expression were observed in resistant cells compared to the parental line.
- Verapamil partially reversed multidrug resistance, with varying sensitization rates for different drugs.
Conclusions:
- A 10-week exposure to colchicine (0.5 microg/ml) effectively induced multidrug resistance in vitro.
- Elevated P-glycoprotein (P-Gp) expression is a likely contributor to the observed drug resistance.
- Partial reversal of MDR by verapamil suggests its potential in overcoming drug resistance in colon cancer.