Enhanced sensitivity to 1-β-D-arabinofuranosylcytosine and topoisomerase II inhibitors in tumor cell lines harboring activated ras oncogenes

Han Mo Koo, Anne Monks, Andrei M Mikheev, Larry V. Rubinstein, Marcia Gray-Goodrich, Mary Jane McWilliams, W. Gregory Alvord, Herbert K. Oie, Adi F. Gazdar, Kenneth D. Paull, Helmut Zarbl, George F. Vande Woude

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

We used human tumor cell lines from the National Cancer Institute's In Vitro Antineoplastic Drug Screen to assess whether sensitivity to ally of the ~45,000 compounds tested previously correlated with the presence of a ras oncogene. Among these cell lines, the mutations in Ki-ras2 clustered in non- small cell lung and colon carcinoma subpanels, and five of the six leukemia lines contained mutations in either N-ras or Ki-ras2. These analyses revealed a striking correlation with 1-β-D-arabinofuranosylcytosine (Ara-C) and 2,2'- O-cyclocytidine sensitivity in the cell lines harboring ras mutations compared to the tumor lines with wild-type ras alleles. Strong correlations were also found with topoisomerase (topo) II inhibitors, especially 3'- hydroxydaunorubicin and an olivacine derivative. These differential sensitivities persisted in an additional 22 non-small cell lung carcinoma lines (ras mutations, n = 12 and wild-type ras, n = 10). Thus, the association with Ara-C sensitivity was greatest while topo II inhibitors showed a lower, but significant, correlation. These results suggest that the ras oncogene may play a determinant role in rendering tumor cells sensitive to deoxycytidine analogues and topo II inhibitors.

Original languageEnglish (US)
Pages (from-to)5211-5216
Number of pages6
JournalCancer research
Volume56
Issue number22
StatePublished - Nov 15 1996

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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