RELATIONSHIP OF INHERENT RESISTANCE TO DOXORUBICIN, PROLIFERATIVE ACTIVITY AND EXPRESSION OF P-GLYCOPROTEIN-170, AND GLUTATHIONE-S-TRANSFERASE-PI IN HUMAN LUNG-TUMORS

Background. 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. Methods. 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. Results. 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 < 0.0001). Expression of P-170 and GST-pi showed highly significant (P < 0.0001) positive correlation. Conclusions. 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.