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.

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.

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