Date of Award
Master of Science
Physiology and Pharmacology
Dr. James Koropatnickcancer, antisense, thymidylate synthase, indoleamine 2,3 dioxygenase, siRNA, RNAi, drug resistance, chemotherapy, immune tolerance, combined therapy
Combining therapeutic agents, as a cancer treatment strategy, using antisense targeting thym idylate synthase (TS) and indoleam ine 2,3-dioxygenase (IDO) can potentially reduce tumour cell proliferation, enhance TS-targeting chemosensitivity and enhance tumour immune recognition. However, it must be determined if one reagent modifies the effectiveness of another. The effects of combining small-interfering RNA (siRNA) targeting TS and IDO on target mRNA levels and sensitivity to TS-targeting and other drugs were investigated. IDO or TS siRNA alone reduced their mRNA targets specifically and without effects on non-target mRNAs. IDO siRNA combined with TS siRNA did not affect TS siRNA knockdown of TS mRNA. TS siRNA, however, reduced the ability of IDO siRNA to down-regulate IDO mRNA. IDO siRNA did not affect TS siRNA- induced specific drug sensitivity. Targeting multiple mRNAs simultaneously may not have the effect predicted by studies involving single siRNAs. These results are
important in determining potential drug combinations in anticancer therapy.
Calonego, Kathleen, "Com bining antisense drugs targeting thym idylate synthase and indoleam ine 2,3-dioxygenase in hum an cancer cells: potentialfor combined therapy" (2009). Digitized Theses. 3852.