Overcoming Autophagy to Induce Apoptosis in Castration Resistant Prostate Cancer
Technical Report,30 Sep 2014,29 Sep 2015
University of California, Davis Davis United States
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In year 3, we took a turn and expanded into the mechanism behind meformin inhibitory effect on prostate cancer cells. In our hands, it was clearly shown that metformin treatment causes AR degradation via ubiquitin degradation. The E3 ligase Skp2 is one of the contributing enzyme for this proteasome degradation. We continues our studies with the in vivo orthotopic GRP-Pro CRPC model. Anti-androgen enzalutamide alone is not the most effective therapy for this neuropeptide-mediated aberrant AR activation model. No tumor growth or PSA production was inhibited. On the other hand, metformin alone is able to sequester almost 50 percent of tumor growth. Combination did not add on much more effect. Lastly, with the CWR22 xenograft model, a well-planned and exhausting effort of drug dosing was abated due to the failure of tumor recurrence after castration. We will revisit this experiment in the no-cost extension period to complete the entire project.