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The Journal of Chemotherapy publishes original experimental and clinical research articles, reviews, brief communications and letters in English on: antivirals, immunomodulators, anticancer drugs, antibiotics, antifungals.
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P E R I O D I C A L O F
February 2006 |
Induced Resistance in the Human Non Small Cell Lung Carcinoma (NCI-H460) Cell Line In Vitro by Anticancer Drugs
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M. PESIC
J.Z. MARKOVIC
D. JANKOVIC
S. KANAZIR
I.D. MARKOVIC
L. RAKIC
S. RUZDIJIC
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.
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