Rapid activation of MDR1 gene expression in human metastatic sarcoma after in vivo exposure to doxorubicin

Amir Abolhoda, Amy E. Wilson, Howard Ross, Peter V. Danenberg, Michael Burt, Kathleen W. Scotto

Research output: Contribution to journalArticlepeer-review

200 Scopus citations

Abstract

Overexpression of P-glycoprotein (Pgp), a multidrug transporter encoded by the MDR1 gene, is associated with chemoresistance in some human solid tumor malignancies. To date, analyses of MDR1 levels in solid tumors have examined constitutive increases in expression at relapse. In the present study, we have evaluated the acute induction of MDR1 gene expression in a solid human tumor as a function of time in response to in vivo exposure to chemotherapy. Five patients with unresectable sarcoma pulmonary metastases underwent isolated single lung perfusion with doxorubicin. Relative MDR1 gene expression was measured in metastatic tumor nodules and normal lung specimens after initiation of chemoperfusion. In four of five patients, a 3-15-fold (median, 6.8) increase in MDR1 RNA levels was detected in tumors at 50 min after administration of doxorubicin. In contrast, normal lung samples had very low levels of MDR1 RNA prior to perfusion, and no acute increases were observed after therapy. These findings demonstrate, for the first time, that MDR1 gene expression can be rapidly activated in human tumors after transient in vivo exposure to cytotoxic chemotherapy.

Original languageEnglish (US)
Pages (from-to)3352-3356
Number of pages5
JournalClinical Cancer Research
Volume5
Issue number11
StatePublished - Nov 1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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