Induced resistance in the human non small cell lung carcinoma (NCI-H460) cell line in vitro by anticancer drugs

J Chemother. 2006 Feb;18(1):66-73. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / adverse effects*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Curcumin / adverse effects
  • Doxorubicin / adverse effects
  • Doxorubicin / pharmacokinetics
  • Drug Resistance, Multiple*
  • Drug Resistance, Neoplasm*
  • Etoposide / adverse effects
  • Glutathione Transferase / metabolism
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Multidrug Resistance-Associated Proteins / genetics
  • Multidrug Resistance-Associated Proteins / metabolism*
  • Paclitaxel / adverse effects
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Rhodamines / metabolism
  • Tumor Cells, Cultured
  • Verapamil / adverse effects
  • Vinblastine / adverse effects


  • Antineoplastic Agents
  • Multidrug Resistance-Associated Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Rhodamines
  • lissamine rhodamine B
  • Vinblastine
  • Etoposide
  • Doxorubicin
  • Verapamil
  • Glutathione Transferase
  • Curcumin
  • Paclitaxel