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.
Institute for Biological Research, Department of Neurobiology and Immunology, Laboratory of Molecular Neurobiology, Belgrade, Serbia & Montenegro.
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M
Pesic
J Z
JZ
Markovic
D
D
Jankovic
S
S
Kanazir
I D
ID
Markovic
L
L
Rakic
S
S
Ruzdijic
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