Effect of Zoledronic Acid on the Sonic-Hedgehog Pathway through Rab GTPase in Prostate Cancer Stem Cells
Project no. 61 · Status: Kapanmış · 2016
Summary
Prostate cancer (PCa) is second most common cancers among cancer-related death after lung cancer in men. Cancer stem cell is a group of cells that they exist slightly in neoplastic tissue and ability proliferation endless by itself and keeping silent such as stem cell. It is thinked that these cells are responsible from cancer proliferation, resistance to the conventional treatments, invasion ve also metastasis. The deregulation of the multiple signaling pathways in the stem cells including the Hh, Wnt, Notch and BMP pathways have been related with the formation and expansion of cancer. SHH signaling plays role in transformation of prostate basal / stem cells into prostate cancer stem cells (PCSCs) and regulates maintance and survival of cancer stem cells. Rab23 GTPase negatively regulated SHH signal pathway in a Sufu-depedent–manner in the healthy tissues. The human prostate cancer cells (Du145 and PC3) were sorted using a FACSAria flow cytometer. Prostate cancer stem cells were sorted to be CD 133high/ CD44high population. IC50 values were found in experimental groups by applying zoledronic acid. To investigate the expression profile of Rab23 GTP and SHH pathway components in the experimental groups treated with zoledronic acid total RNA was extracted using RNeasy Plus Mini Kit ( Qiagen) and this was followed by cDNA synthesis and expression were analyses by LightCycler® 480 real-time PCR. On the results, the expression profile of The results were compared between zoledronic administered human prostate CSCs and control groups. This study has been the first to characterize the effect of Zoledronic acid on the ability of Rab23 GTPase and SHH pathway components and consequently on CSCs properties.