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 less than 0.0001). Expression of P-170 and GST-pi showed highly significant (P less than 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.
Department of Experimental Pathology, German Cancer Research Center, Heidelberg.
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M
Volm
J
J
Mattern
B
B
Samsel
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000328:Adult; D000368:Aged; D001706:Biopsy; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000201:enzymology / Q000473:pathology*; D002455:Cell Division / Q000502:physiology; D004317:Doxorubicin / Q000494:pharmacology*; D004351:Drug Resistance; D005260:Female; D005982:Glutathione Transferase / Q000032:analysis / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis / Q000502:physiology*; D008175:Lung Neoplasms / Q000737:chemistry / Q000201:enzymology / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000502:physiology*; D008875:Middle Aged; D013936:Thymidine / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D004317:Doxorubicin; D005982:Glutathione Transferase; D013936:Thymidine