P-glycoprotein-mediated multidrug resistance and cytotoxic effector cells.
Multidrug resistance (MDR) is one of the major obstacles to successful cancer chemotherapy. MDR is a complex and multifactorial phenomenon. One important and common mechanism used by cancer cells as a defense against cytotoxic drugs is a 170-kD plasma membrane glycoprotein, P-glycoprotein (P-gp). P-gp confers resistance by actively pumping cytotoxic drugs out of cancer cells. Paradoxically, P-gp overexpression on tumor cells is frequently associated with enhanced susceptibility to lymphokine-activated killer cell activity. This enhanced susceptibility is not observed with P-gp- MDR cells, nor is susceptibility to natural killer cells increased. The physiologic, evolutionary and immunologic concepts with regard to the P-gp and the possible intervention of the function of the P-gp in cancer therapy are reviewed.
Savas
B
B
Department of Microbiology and Immunology, Queen's University, Kingston, Canada.
Cole
S P
SP
Akoglu
T F
TF
Pross
H F
HF
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004351:Drug Resistance / Q000276:immunology; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D009369:Neoplasms / Q000188:drug therapy
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins