Establishing a Role for Ecto-Phosphatases in Multidrug Resistance in Breast Cancer
Final rept. 1 Oct 2000-30 Sep 2001
TEXAS UNIV AT AUSTIN
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Multi Drug Resistance MDR is a phenomenon where tumor cells treated with one chemotherapeutic agent become resistant to many unrelated drugs. It is thought that most cancer MDR is due to the upregulation of drug efflux proteins, such as MDR1 or BCRP. We previously showed that ecto-phosphatase upregulation can lead to an MDR phenotype and ecto-phosphatase inhibition leads to breakdown of p-glycoprotein-mediated MDR implicating ecto-phosphatase activity as a second component of MDR. The experiments here, tested whether novel ecto-phosphatase inhibitors, added to the media, lowers the minimum inhibitory drug concentration MIC of non-drug resistant breast cancer cell lines or lowers the drug resistance of MDR lines. The hypothesis tested is that apyrase and other ecto-phosphatases are potential chemotherapeutic targets for the treatment of MDR cancers. These studies showed that there was no reduction in MIC for non drug resistant or drug resistant breast cancer cell lines. The long-term goal is to provide new tools to fight the growing problem of drug-resistant cancers by targeting drug efflux. Based on these exploratory experiments, it is concluded that ecto phosphatase activity alone is probably not a viable anti MDR target in breast cancer.
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