Multidrug-resistant gene expression in small-cell lung cancer

Niramol Savaraj, Chun Jing Wu, Rong Xu, Theodore Lampidis, Shenghan Lai, Elizabeth Donnelly, Jeanine Solomon, Lynn G. Feun

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Abstract

The development of drug resistance can contribute to treatment failure in small-cell lung cancer (SCLC). In this report, we investigate p- glycoprotein-mediated multidrug resistance (MDR) in these patients. Tumor tissue was obtained prior to treatment and at relapse if possible, short- term culture was carried out, and these tumor cells were analyzed for MDR gene expression by slot blot and reverse transcriptase polymerase chain reaction (RT-PCR) and northern blot analysis. Three cell lines were also established from short-term cultures. Twenty-four patients with MDR(-) and seven with MDR+(++) were available for survivaI analysis. Median survival for MDR(-) patients was 10 months, whereas for MDR+(++) patients it was 2 months. This was statistically significance (p < 0.0007). The presence of MDR 1 gene expression also correlated with the lack of response to chemotherapy (p < 0.001). Increased MDR1 gene expression is usually present in patients with more tumor burden at initial diagnosis. Furthermore, loss of MDR1 gene expression can occur in intrinsically MDR(+) SCLC cells after multiple passages in drug-free media. We concluded that increased MDR1 gone expression is present in a small number of SCLC both before and after chemotherapy and usually signifies poor survival and no response to chemotherapy.

Original languageEnglish (US)
Pages (from-to)398-403
Number of pages6
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume20
Issue number4
DOIs
StatePublished - Aug 1 1997

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Keywords

  • MDR gene
  • Small-cell lung cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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