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Research Paper
Contributing Factors of Temozolomide Resistance in MCF-7 Tumor Xenograft Models
Yoshinori Kato, Baasil Okollie, Venu Raman, Farhad Vesuna, Ming Zhao, Sharyn D. Baker, Zaver M. Bhujwalla and Dmitri Artemov
volume 6 | issue 6
June 2007We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.
Vasculature mediated drug resistance in tumors was studied in female SCID mice bearing wild type MCF-7 and adriamycin resistant MCF-7/ADR xenograft using temozolomide (TMZ). A strong tumor growth inhibitory effect of TMZ treatment was 5 observed in MCF-7 tumors during the initial treatment phase with subsequent relapse, but not in MCF-7/ADR tumors. Non-invasive MRI measurements of tumor vascular volume and vascular permeability-surface area product (PS) demonstrated significant reduction of PS in long-term treated MCF-7, but not in MCF-7/ADR tumors. O6-Methylguanine-DNA methyltransferase (MGMT) mRNA, and VEGF expression 10 was analyzed using real-time RT-PCR and ELISA, respectively. No significant changes in MGMT mRNA and VEGF expression were observed in either MCF-7 or MCF-7/ADR tumors. However, in vitro incubation of MCF-7 cells with TMZ did induce the expression of MGMT mRNA. In addition, p53 and p21 levels were scored by immunoblotting. Exposure of cells to TMZ did not affect either the p21 or 15 the p53 expression in both MCF-7 and MCF-7/ADR cells. The absence of these molecular responses to TMZ treatment in MCF-7 tumors in vivo supports the possibility that the onset of cancer drug resistance is associated with reduced PS, which can decrease the delivery of the drug to the cancer cells.
Authors
Yoshinori Kato
The Johns Hopkins University School of Medicine, Baltimore, MD USA
Baasil Okollie
The Johns Hopkins University School of Medicine, Baltimore, MD USA
Venu Raman
Johns Hopkins University, School of Medicine; Baltimore MD USA
Farhad Vesuna
Johns Hopkins University, School of Medicine; Baltimore MD USA
Ming Zhao
Johns Hopkins University, School of Medicine; Baltimore MD USA
Sharyn D. Baker
Johns Hopkins University, School of Medicine; Baltimore MD USA
Zaver M. Bhujwalla
Johns Hopkins University, School of Medicine; Baltimore MD USA
Dmitri Artemov
Johns Hopkins University, School of Medicine; Baltimore MD USA
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.