Relationship of inherent resistance to doxorubicin, proliferative activity and expression of P-glycoprotein 170, and glutathione S-transferase-pi in human lung tumors.

Abstract

This study analyzed whether proliferative activity and expression of P-glycoprotein 170 (P-170) or glutathione S-transferase-pi (GST-pi) in human non-small cell lung carcinomas (NSCLC) represent independent factors in resistance to doxorubicin or whether an association exists between these factors. Thirty-six patients with previously untreated NSCLC participated in the study. The thymidine labelling index (TLI) was measured for detection of proliferative activity, and immunohistochemistry was used for detection of P-170 and GST-pi. The resistance of tumors was determined in vitro by the nucleotide incorporation assay. Negative correlations between TLI and P-170 (P = 0.0009) or GST-pi (P = 0.007) were found. Positive correlations existed between resistance to doxorubicin in vitro and P-170 (P = 0.005) or GST-pi (P less than 0.0001). Expression of P-170 and GST-pi showed highly significant (P less than 0.0001) positive correlation. The results demonstrate that a significant positive relationship between P-170 and GST-pi in NSCLC exists and that the expression is increased in resistant tumors and in tumors with a low proliferative activity.