Inhibiting Cancer Glucose Metabolism Using Metformin and MCT4 Antisense Oligonucleotides
York House School
Floor Location : S 234 H
Prostate Cancer is the second most common cancer in men, and currently there is no curative therapy once the cancer has metastasized. Thus, the objective of this project was to develop a more effective therapy against Prostate Cancer by targeting two major ATP production pathways in combination: glycolysis (by using antisense oligonucleotides [ASO] to target monocarboxylate transporter 4 [MCT4]) and the tricarboxylic acid (TCA) cycle (by using metformin). The goals were to 1) identify an effective and appropriate concentration of Metformin to be used in combination with our MCT4 ASO developed in the lab, and 2) inhibit cancer growth using both therapeutic agents together. Prostate cancer cells were cultured and treated with MCT4 ASO, metformin, and together in combination. The effectiveness was measured by counting cell numbers and determining mRNA expression levels by qPCR. I found that MCT4 ASO can successfully reduce prostate cancer cell numbers, and similarly, metformin proved to be effective; increasing concentrations of metformin was significantly associated with more cell death. Furthermore, the combination of MCT4 ASO and metformin showed a greater effect in inhibiting cell proliferation. Our results demonstrate that co-targeting glycolysis and the TCA cycle prove to be a more effective strategy for treatment of advanced prostate cancer.