ASSOCIATED EXPRESSION OF PROTEIN-KINASE-C WITH RESISTANCE TO DOXORUBICIN IN HUMAN LUNG-CANCER

The expression of protein kinase C (PKC) in 83 untreated solid human n on-small cell lung carcinomas was determined and its correlation with inherent resistance to doxorubicin, with the expression of P-glycoprot ein (P-170), and with the expression of glutathione S-transferase-pi ( GST-pi) was analysed. Doxorubicin resistance was measured using an in vitro short-term test. The expression of PKC, P-170 and GST-pi was ass essed immunohistochemically. Twenty-three tumors (=28%) were PKC-posit ive, whereas 60 tumors (=72%) were PKC-negative. Nineteen tumors (=23% ) were classified as sensitive and 64 tumors (=77%) as resistant to do xorubicin. Thirty-nine tumors (=47%) were P-170-positive and 51 tumors (=61%) GST-pi-positive. Out of the PKC-positive tumors, 21 were resis tant to doxorubicin and 2 were sensitive. Of the same 23 tumors, 18 we re P-170-positive and 19 were GST-pi-positive. The correlations betwee n the expression of PKC and the resistance to doxorubicin, the express ion of P-170 and the expression of GST-pi were statistically significa nt. Corresponding results were obtained comparing the results of all t umors with the results of a subgroup of tumors having the same histolo gy (squamous cell carcinomas). This supports the hypothesis that PKC i s involved in the inherent doxorubicin-resistance of human lung cancer .