Date of Award
2006
Degree Type
Thesis
Degree Name
Master of Science
Program
Microbiology and Immunology
Supervisor
Dr. Jim Koropatnick
Second Advisor
Dr. Joe Mymryk
Third Advisor
Dr. Robert Hudson
Abstract
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.
Recommended Citation
Randvra, Aleksandra A., "COMBINATION siRNA TARGETING BCL-2 ANTAGONIZES siRNA AGAINST THYMIDYLATE SYNTHASE (TS) IN HUMAN TUMOR CELL LINES" (2006). Digitized Theses. 4885.
https://ir.lib.uwo.ca/digitizedtheses/4885