Title

Establishment of in Vivo and in Virto Systems to Study Efficacy of Doxorubicin in the PyVT Breast Cancer Mouse Model

Publication Year

2005

Keywords

Doxorubicin, chemotherapy treatment, cells, cancer

Disciplines

Biology | Cancer Biology | Cell and Developmental Biology | Life Sciences

Abstract

Cancer is a disease of uncontrolled cell growth that affects 40 percent of Americans. Several forms of treatment have been developed including chemotherapy, which is the use of agents to inhibit cellular proliferation. Doxorubicin (DOX) is one of the most effective chemotherapy drugs; however, it is limited by the side effect of cardiac toxicity. This toxicity is due to the conversion of DOX to doxorubicinol by carbonyl reductase 1 (CBR1). Mice with a null copy of Cbr1 exhibit reduced cardiac toxicity. This research established in vivo and in vtro systems to study the effect of Cbr1 on DOX efficacy, with the hypothesis that chemotherapeutic efficacy would be enhanced in mice with a null copy of Cbr1. In vivo studies focused on tumor regression in the PyVT breast cancer mouse model in response to DOX administration. Preliminary baseline data has established that the dosage of DOX used in this protocol is both effective in the reduction of tumor burden and well-tolerated by the PyVT oncogenic animals. In vitro studies examined a DOX dose-dependent response assay in cell culture. Tumor explanation experimentation established primary PyVT Cbr1 +/+ cell lines. Examination of cytotoxicity in one of these cell lines was performed via DOX incubation and the MTS assay for detection. Both in vivo and in vitro systems will be used to examine the effect of the Cbr1 null allele in future experimentation. Enhanced tumor regression and cytotoxicity is anticipated in Cbr1 +/- mouse models and cell lines respectively. If this is true, an inhibitor of Cbr1 would have clinical benefit in patients undergoing chemotherapy.

Department 1 Awarding Honors Status

Biology

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