Treatment of human ovarian tumor xenografts with selenite prevents the melphalan-induced development of drug resistance.
Human ovarian tumors (derived from A2780 cells), growing as subcutaneous xenografts in immunodeficient mice, develop melphalan-resistant cells after a single treatment of the tumor-bearing animal with the drug [Caffrey, Zhang and Frenkel, submitted for publication]. Treatment of the animals with selenite by i.p. injection prevented the development of primary resistance to melphalan as well as cross-resistance to cisplatin. Selenite treatment also prevented the melphalan-induced increase in the cellular level of glutathione. In contrast, selenite administered s.c. or in drinking water had relatively little effect on the development of resistance. The results in this animal model suggest that selenite may be clinically useful in preventing the development of drug resistance during chemotherapy of cancer.
Caffrey
P B
PB
Department of Biological Sciences, Rutgers University, Newark, NJ 07102, USA.
Frenkel
G D
GD
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology; D004347:Drug Interactions; D019008:Drug Resistance, Neoplasm; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008558:Melphalan / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D018038:Sodium Selenite / Q000494:pharmacology*; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D005978:Glutathione; D018038:Sodium Selenite; D002945:Cisplatin; D008558:Melphalan