The major goal of this proposal is to test whether depletion of PLK1 will reduce the cell viability of Pim-1 overexpressing cells and whether the combination of chemotherapeutic reagents with PLK1 depletion will enhance drug sensitivity in a synergistic manner in Pim-1 overexpressing prostate cells. As such, this study is expected to provide a novel alternative therapeutic target for prostate cancer. This study has an excellent chance of providing results with clear clinical significance that may lead to better treatment options for cancer patients. To achieve our goal, the following specific aims are proposed. SPECIFIC AIM 1: To examine whether depletion of PLK1 results in synthetic lethality in Pim-1 overexpressing cells. 1A. We will test whether loss of PLK1 reduces the viability of Pim-1 overexpressing prostate cells using individual siRNAs against PLK1, and then the expression level of PLK1 will be measured by quantitative RT-PCR (qRT-PCR) and Western blotting analysis. 1B. We will examine the mechanistic basis of reduced cell viability of Pim-1 overexpreesing prostate cells after PLK1 depletion by checking proliferation, apoptosis, cell cycle distribution and mitotic machinery. 1C. We will test whether Pim-1 overexpressing cells lose tumorigenicity after PLK1 depletion by performing in vitro soft agar and in vivo xenograft assays. SPECIFIC AIM 2: To test whether depletion of PLK1 further sensitizes Pim-1 overexpressing cells to prostate cancer drugs. 2A. We will test whether loss of PLK1 can synergize with prostate cancer drugs in Pim-1 overexpressing prostate cells. 2B. We will examine the mechanistic basis of the synergistic effect of PLK1 depletion with prostate cancer drugs by checking proliferation, apoptosis, cell cycle distribution and mitotic machinery in Pim-1 overexpressing prostate cells. 2C. We will test whether Pim-1 overexpressing cells further lose tumorigenicity after PLK1 depletion in combination with prostate cancer drugs by performing in vitro soft agar and in vivo xenograft assays.
|Effective start/end date||4/8/14 → 8/14/14|
- U.S. Army Medical Research and Materiel Command (W81XWH-10-1-0246)
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