Characterisation of a mouse tumour cell line with in vitro derived resistance to verapamil

Br J Cancer. 1990 Feb;61(2):279-84. doi: 10.1038/bjc.1990.52.


We have established a subline (EMT6/VRP) of the mouse tumour cell line EMT6/P with acquired resistance to the calcium transport blocker verapamil (VRP). The subline was 4-fold resistant to the cytoxicity of VRP alone compared with the parent line but of similar sensitivity to adriamycin, vincristine or colchicine. EMT6/VRP cells growing in 75 micrograms ml-1 VRP were morphologically different from and larger in diameter than EMT6/P cells, but these two parameters reverted almost to normal within 3 days of VRP removal, although resistance was retained. Expression of an mRNA coding for P-glycoprotein was similar in EMT6/VRP and the parent cell line, although considerable hyperexpression was seen in a multidrug resistant subline, EMT6/AR1.0. Cellular accumulation of both 3H-daunorubicin and 3H-VRP were greater in EMT6/VRP than in the parent line. Sensitisation to adriamycin by 3.3 micrograms ml-1 VRP was, however, somewhat reduced in EMT6/VRP (i.e. to 6.1-fold) compared with the 11-fold sensitisation seen in the parent line. It is clear that resistance to VRP seen in this cell line occurs via a different mechanism from the resistance to drugs such as adriamycin, vincristine and colchicine seen in multidrug resistant cell lines.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Animals
  • Cell Line
  • Colchicine / pharmacology
  • DNA, Neoplasm / analysis
  • Doxorubicin / pharmacology
  • Drug Resistance
  • Drug Screening Assays, Antitumor
  • Membrane Glycoproteins / genetics
  • Mice
  • Tumor Cells, Cultured / drug effects*
  • Tumor Cells, Cultured / pathology
  • Verapamil / pharmacology*
  • Vincristine / pharmacology


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • DNA, Neoplasm
  • Membrane Glycoproteins
  • Vincristine
  • Doxorubicin
  • Verapamil
  • Colchicine