Induced Resistance in the Human Non Small Cell Lung Carcinoma (NCI-H460) Cell Line In Vitro by Anticancer Drugs

• Published in: Journal of chemotherapy (Florence) 2006-02, Vol.18 (1), p.66-73
• Main Authors: Pesic, M., Markovic, J.Z., Jankovic, D., Kanazir, S., Markovic, I.D., Rakic, L., Ruzdijic, S.
• Format: Article
• Language: English
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antineoplastic Agents - adverse effects; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; curcumin; Curcumin - adverse effects; doxorubicin; Doxorubicin - adverse effects; Doxorubicin - pharmacokinetics; doxorubicin efflux; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Etoposide - adverse effects; Glutathione Transferase - metabolism; glutathione-S-transferase; Human non-small cell lung carcinoma (NSCLC); Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Medical sciences; multidrug resistance; Multidrug Resistance-Associated Proteins - genetics; Multidrug Resistance-Associated Proteins - metabolism; P-glycoprotein; pacilitaxel; Paclitaxel - adverse effects; Pharmacology. Drug treatments; Pneumology; Rhodamines - metabolism; RNA, Messenger - drug effects; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Neoplasm - genetics; RNA, Neoplasm - metabolism; RT-PCR; Tumor Cells, Cultured; Tumors of the respiratory system and mediastinum; verapamil; Verapamil - adverse effects; Vinblastine - adverse effects
• ISSN: 1120-009X; 1973-9478
• DOI: 10.1179/joc.2006.18.1.66

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.