Relationship of inherent resistance to doxorubicin, proliferative activity and expression of P-glycoprotein 170, and glutathione S-transf erase-π in human lung tumors

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Abstract
Background. This study analyzed whether proliferative activity and expression of P‐glycoprotein 170 (P‐170) or glutathione S‐transferase‐π (GST‐π) 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‐π. 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‐π (P = 0.007) were found. Positive correlations existed between resistance to doxorubicin in vitro and P‐170 (P = 0.005) or GST‐π (P < 0.0001). Expression of P‐170 and GST‐π showed highly significant (P < 0.0001) positive correlation. Conclusions. The results demonstrate that a significant positive relationship between P‐170 and GST‐π in NSCLC exists and that the expression is increased in resistant tumors and in tumors with a low proliferative activity. Cancer 1992; 70:764–769.

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