Anticancer drug resistance of HeLa cells transfected with rat glutathione S-transferase pi gene

Biomed Environ Sci. 2003 Jun;16(2):157-62.

Abstract

Objective: To establish a cytologic expressing system of rat glutathione S-transferase pi (GST-pi) cDNA for detecting the resistance of HeLa cells to anticancer drugs.

Methods: The assessment was made with various anticancer drugs (adriamycin, mitomycin, cisplatinum and vincristine) that showed different cytotoxicities in transfectant HeLa cells with pSV-GT containing rat GST-pi cDNA (HeLa/pSV-GT) or control pSV-neo (HeLa/pSV-neo). Expression levels of GST-pi mRNA in HeLa/pSV-GT and HeLa/pSV-neo were measured by in situ hybridization using Digoxin-labelled cDNA probe.

Results: HeLa/pSV-GT expressed significantly high degree of GST-pi mRNA, whereas both HeLa/pSV-neo and HeLa cells had very low expression. Cytotoxicities of HeLa/pSV-GT and HeLa/pSV-neo with 4 anticancer drugs were measured by MTT assay. Drug concentrations for yielding 50% inhibition (IC50) in HeLa/pSV-GT by adriamycin, mitomycin and cisplatinum were 70.13 microg/mL, 10.95 microg/mL and 16.52 microg/mL, respectively. In contrast, IC50 in HeLa/pSV-neo was 10.34 microg/mL, 7.48 microg/mL and 13.70 microg/mL, respectively. The cytotoxicities of vincristine on both HeLa/pSV-GT and HeLa/pSV-neo were not significantly different.

Conclusions: Our findings suggest that HeLa/pSV-GT containing rat GST-pi cDNA is resistant to some anticancer drugs due to overexpression of GST-pi. Also, HeLa/pSV-GT cell line could serve as a useful cytogenetic model for further research.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • DNA, Complementary
  • Drug Resistance
  • Drug Screening Assays, Antitumor
  • Glutathione Transferase / biosynthesis*
  • Glutathione Transferase / pharmacology*
  • HeLa Cells
  • Humans
  • Rats
  • Transfection*

Substances

  • Antineoplastic Agents
  • DNA, Complementary
  • Glutathione Transferase