The role of p-glycoprotein, glutathione-s-transferase-pi, thymidylate synthase and metallothionein in the expression of differential sensitivities to antitumor agents in human tumor xenografts.

Expression of P-glycoprotein (P-gp), glutathione S-transferase-pi (GST-pi), thymidylate synthase (TS) and metallothionein (MT) was studied in a series of different human tumors growing in nude mice and expressing a range of in vivo sensitivities to certain antitumor agents. Quantitative relationships between resistance parameters and sensitivities to seven clinically used antitumor drugs in vivo, as judged by specific growth delay, were determined by Wilcoxon test. A positive relationship was identified between expression of GST-pi and TS and sensitivities to cyclophosphamide, doxorubicin, and 5-fluorouracil. No relationship was noted between MT expression and P-gp expression and any of these drug sensitivities in this series of tumors.