Date of Award


Degree Type


Degree Name

Master of Science


Microbiology and Immunology


Dr. Jim Koropatnick

Second Advisor

Dr. Joe Mymryk

Third Advisor

Dr. Robert Hudson


To assess the simultaneous targeting of a proliferation-associated and pro-survival molecule as a potential chemotherapeutic strategy, I investigated the effects of siRNA targeting both thymidylate synthase (TS) and Bcl-2 in HeLa and MCF-7 cell lines. I report that treatment of HeLa and MCF-7 cells with TS and Bcl-2 siRNAs had unexpected, antagonistic effects. One of the Bcl-2 siRNAs reduced the capacity of TS siRNA to decrease TS mRNA and protein, and treatment of HeLa cells with this Bcl-2 siRNA alone resulted in increased TS mRNA and protein. Pretreatment with TS siRNA sensitized HeLa and MCF-7 cells to TS-targeting drugs, but addition of antagonistic Bcl-2 siRNA abrogated sensitization and addition of the non-antagonistic Bcl-2 siRNA did not increase sensitization. Combined targeting of separate physiological pathways by antisense reagents may be a useful approach in treatment of cancer, but antagonistic interactions could abrogate advantages or reduce effectiveness of other agents.



To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.