Patterns of cross-resistance in a multidrug-resistant small-cell lung carcinoma cell line

Cancer Chemother Pharmacol. 1990;26(4):250-6. doi: 10.1007/BF02897225.


H69AR is a multidrug-resistant human small-cell lung carcinoma cell line that was selected in doxorubicin and has previously been shown to be cross-resistant to a variety of natural-product-type anticancer drugs. H69AR is unlike many other multidrug-resistant cell lines in that it does not overexpress P-glycoprotein. In the present study, the drug sensitivity and cross-resistance patterns of H69AR cells were further characterized. A total of 15 drugs belonging to a number of chemical classes were screened. These compounds included anthracyclines, DNA binders (anthrapyrazoles, benzothiopyranoindazoles, and pyrazoloacridines), and lipophilic antifolates. The alkylating agent melphalan and the antimetabolite cytosine arabinofuranoside (Ara-C) were also tested. In general, the drug sensitivity and cross-resistance profiles of H69AR cells were consistent with those reported by others using other drug-resistant cell lines. However, there were several unexpected instances of cross-resistance. Thus, the H69AR cell line was more resistant than its parent cell line to the potent 3'-deamino-3'-(3-cyano-4-morpholinyl) doxorubicin, bisantrene, the pyrazoloacridine PD 114541, Ara-C, and melphalan. In addition, no cross-resistance to the four lipophilic antifolates tested, including trimetrexate, was found. The absence of a consistent pattern among the various drug-resistant cell lines indicates that assumptions about the efficacy of anticancer drugs in multidrug resistance should be made with caution.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antibiotics, Antineoplastic / pharmacology
  • Antimetabolites / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Carcinoma, Small Cell / genetics*
  • Cell Division / drug effects
  • Drug Resistance / genetics
  • Humans
  • Lung Neoplasms / genetics*
  • Membrane Glycoproteins / physiology
  • Pyrazoles / pharmacology
  • Structure-Activity Relationship
  • Tumor Cells, Cultured / drug effects


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antibiotics, Antineoplastic
  • Antimetabolites
  • Membrane Glycoproteins
  • Pyrazoles