Defense Date

2014

Document Type

Thesis

Degree Name

Master of Science

Department

Pharmacology & Toxicology

First Advisor

DAVID GEWIRTZ

Abstract

In general, ionizing radiation promotes cytoprotective autophagy in a majority of breast tumor cells. Previous studies from our laboratory indicated that radiation (5x2 Gy) induces cytoprotective autophagy in MCF-7 cells. In the current work, inhibition of autophagy by silencing of Beclin-1 in MCF-7 cells resulted in an increase in sensitivity to radiation based both on cell number and clonogenic survival; however, there was no increase in apoptosis and the basis for this sensitization is currently under investigation. Unexpectedly, enhancement of autophagy by silencing of Bcl-2 also led to an increase in sensitivity to radiation, possibly through the conversion of cytoprotective to cytostatic autophagy. In contrast to the MCF-7 cells, radiation (5x2 Gy) induces non-protective autophagy in Hs578t cells. Interference with autophagy through silencing of Beclin-1 or induction of Bcl-2 did not alter radiation sensitivity in the Hs578t cells. Since the induction of cytoprotective autophagy can represent an impediment to radiation therapy, it is important to understand the types of autophagy that occur in response to radiation in specific cellular settings and whether interference with autophagy can increase sensitivity to different forms of cancer treatment.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

May 2014

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