Induced resistance in the human non small cell lung carcinoma (NCI-H460) cell line in vitro by anticancer drugs.
Exposure 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.
Pesic
M
M
Institute for Biological Research, Department of Neurobiology and Immunology, Laboratory of Molecular Neurobiology, Belgrade, Serbia & Montenegro.
Markovic
J Z
JZ
Jankovic
D
D
Kanazir
S
S
Markovic
I D
ID
Rakic
L
L
Ruzdijic
S
S
D000970:Antineoplastic Agents / Q000009:adverse effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003474:Curcumin / Q000009:adverse effects; D004317:Doxorubicin / Q000009:adverse effects / Q000493:pharmacokinetics; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000009:adverse effects; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D017239:Paclitaxel / Q000009:adverse effects; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D012235:Rhodamines / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000009:adverse effects; D014747:Vinblastine / Q000009:adverse effects
D000970:Antineoplastic Agents; D003474:Curcumin; D004317:Doxorubicin; D005047:Etoposide; D005982:Glutathione Transferase; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D017239:Paclitaxel; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D012235:Rhodamines; D014700:Verapamil; D014747:Vinblastine; C022027:lissamine rhodamine B