Pesic, M. (36768679400)M. (36768679400)PesicMarkovic, J.Z. (12139327800)J.Z. (12139327800)MarkovicJankovic, D. (7006385067)D. (7006385067)JankovicKanazir, S. (55961654200)S. (55961654200)KanazirMarkovic, I.D. (7004033826)I.D. (7004033826)MarkovicRakic, L. (35580670800)L. (35580670800)RakicRuzdijic, Sabera (7003935669)Sabera (7003935669)Ruzdijic2025-06-132025-06-132006https://doi.org/10.1179/joc.2006.18.1.66https://www.scopus.com/inward/record.uri?eid=2-s2.0-33645109974&doi=10.1179%2fjoc.2006.18.1.66&partnerID=40&md5=eadc4eeefcecee1781f5bfcf229f3038https://remedy.med.bg.ac.rs/handle/123456789/10956Exposure of human non-small cell lung cancer cells (NCI-H460) to gradually increasing concentrations of doxorubicin resulted in the appearance of a new cell line (NCI-H460/R) that was resistant to doxorubicin (96.2-fold) and cross-resistant to etoposide, paclitaxel, vinblastine and epirubicin. Slight cross-resistance to two MDR-unrelated drugs 8-Cl-cAMP and sulfinosine was observed. Flow cytometry analysis showed that the accumulation of doxorubicin in the resistant cells was 88.4% lower than in the parental cells. Also, verapamil significantly decreased the efflux rate in NCI-H460 and NCI-H460/R cells, whereas curcumin inhibited the efflux in NCI-H460 cells only. Gene expression data confirmed the induction of mdr1 (P-gp), as judged by the observed 15-fold increase in its mRNA concentration in doxorubicin-resistant NCI-H460/R cells. In contrast, mrp1 and lrp expression was unaffected by the doxorubicin resistance. Further work should develop a rationale for a novel treatment of NSCLC with appropriate modulators of resistance aimed at improving the outcome of the acquired drug resistance. © E.S.I.F.T. srl.CurcuminDoxorubicinDoxorubicin effluxGlutathione-S-transferaseHuman non-small cell lung carcinoma (NSCLC)Multidrug resistanceP-glycoproteinPacilitaxelRT-PCRVerapamil