Verapamil and cyclosporin A sensitize human kidney tumor cells to vincristine in absence of membrane P-glycoprotein and without apparent changes in the cytoplasmic free Ca2+ concentration

Biosci Rep. 1990 Apr;10(2):231-7. doi: 10.1007/BF01116583.

Abstract

Vincristine (Vcr) dose dependently inhibited growth of the kidney adenocarcinoma cell line ACHN during 4 days of culture. Verapamil (Ver) at 10 microM and cyclosporin A (CsA) at 1 microgram/ml had no effect on cell growth but significantly potentiated the action of Vcr, despite the absence of the multidrug resistance associated membrane P-glycoprotein (P-gp). Neither Ver nor CsA had any acute or long term effects on cytoplasmic free Ca2+ concentration (Ca2+i), except for a small Ver induced increase after 36 h of incubation. The results indicate that Ver and CsA may have a sensitizing effect on chemotherapeutic drug sensitivity also in absence of P-gp. However, these effects are probably not mediated by changes in Ca2+i.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Calcium / metabolism
  • Cell Division / drug effects
  • Cyclosporins / pharmacology*
  • Cytoplasm / metabolism
  • Dose-Response Relationship, Drug
  • Humans
  • Immunohistochemistry
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology*
  • Membrane Glycoproteins / metabolism*
  • Neoplasm Proteins / metabolism
  • Tumor Cells, Cultured
  • Verapamil / pharmacology*
  • Vincristine / pharmacology*

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Cyclosporins
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • Vincristine
  • Verapamil
  • Calcium