Doxorubicin resistance in a small cell lung cancer cell line can be abolished by siRNA down-regulation of cox 1

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dc.contributor.advisor Vann, Carolyn N. en_US Aryal, Pratik en_US 2011-06-03T19:41:19Z 2011-06-03T19:41:19Z 2007 en_US 2007
dc.identifier LD2489.Z78 2007 .A79 en_US
dc.description.abstract Multidrug resistance (MDR) in small cell lung cancer is one of the major causes of failures of chemotherapy. MDR is a means of protection of tumor cells against chemotherapeutic drugs. Although the molecular basis of MDR is not fully understood, genes involved in apoptosis may be mutated. Recent finding of a link between over-expression of an apoptotic gene, cyclooxygenase 1 (cox 1), and MDR suggests that cox 1 is involved in the development of MDR phenotype. This research was an attempt to observe whether up-regulation of cox 1 contributes to the MDR phenotype in small cell lung cancer cells. This research ultimately may provide a mechanism to reverse the abberant up-regulation of apoptosis genes associated with multidrug resistance to either eliminate or control reproduction of cancer cells. Real time RT PCR was used to confirm the up-regulation of cox 1 in cultured MDR resistant small cell lung cancer cells (GLC4). The up-regulated cox 1 expression was down-regulated using RNA interference technology (RNAi) by transfection with an anti-cox 1 siRNA. More than 90% transfection of cells was confirmed using confocal microscopy. Down-regulation of cox 1 was validated as the protein expression significantly decreased (P=0.004) from multidrug resistant small cell lung cancer transfected cells compared to multidrug resistant nontransfected cells. There was decrease level of expression of cox 1 in multidrug resistant cells after the knockdown with siRNA specific to cox 1. The decreased level of cox 1 expression and, therefore, Cox 1 production increased the rate of apoptosis in small cell lung cancer cells as indicated by its sensitivity to the doxorubicin.
dc.description.sponsorship Department of Biology
dc.format.extent 51 leaves : ill. (chiefly col.) ; 28 cm. en_US
dc.source Virtual Press en_US
dc.subject.lcsh Doxorubicin -- Effectiveness. en_US
dc.subject.lcsh Drug resistance in cancer cells. en_US
dc.subject.lcsh Small cell lung cancer -- Genetic aspects. en_US
dc.subject.lcsh Cyclooxygenases -- Inhibitors. en_US
dc.subject.lcsh Gene silencing. en_US
dc.title Doxorubicin resistance in a small cell lung cancer cell line can be abolished by siRNA down-regulation of cox 1 en_US Thesis (M.S.)
dc.identifier.cardcat-url en_US

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  • Master's Theses [5330]
    Master's theses submitted to the Graduate School by Ball State University master's degree candidates in partial fulfillment of degree requirements.

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