报告题目：Understand the role of P2X4 receptor in prostate cancer

报告人：Ning Wang 谢菲尔德大学

主持人：罗剑 教授

报告时间：2019年12月6日 上午10:50（周五上午）

报告地点：生命科学学院534小会议室

报告人简介：

Dr Ning Wang is a cancer biologist interested in cancer induced bone diseases and cancer cell dormancy. Dr Wang undertook his undergraduate (BSc) and postgraduate (MRes) training in biology at Ocean University of China. After moving to the UK in 2004, he studied the trend of Biotech-industry development at Loughborough University and gained his MSc in Management the following year. He then joined Professor Alison Gartland’s group in Sheffield and was awarded his PhD in 2010 for his contribution in investigating the roles of purinergic signalling in osteoporosis. Dr Wang was subsequently appointed as a Post-doctoral Research Associate in Dr Colby Eaton’s lab in 2010 and a Senior Post-doctoral Research Associate in Professor Tim Skerry’s group in 2014. He is now the Group Leader and Principle Investigator of the Mechanobiology and Cancer Biology group, University of Sheffield. His current main research interests focus on defining impact of exercise on the initiation and progression of prostate/breast cancer skeletal metastasis using pre-clinical models, which are supported by the Prostate Cancer UK Research Innovation Award and Weston Park Cancer Charity Large Grant. His research also receives sponsor from The Royal Society and Mexican CONACyT scholarship. Over the past five years, he has authored more than 20 publications (14 articles as first and/or correspondent author, citation>400, h-index: 13) in high impact peer reviewed journals such as J Bone Miner Res, FASEB J, Stem Cell, Clin Cancer Res etc. Being a newly elected member of the prestigious ECTS Academy, he has demonstrated his increasing national and international profile. He regularly referees papers for peer-reviewed international journals (e.g. JBMR, Int J Cancer, Bone, and Sci Rep etc) and reviews grant applications for international funding bodies such as KWF Kankerbestrijding – Dutch Cancer Society (DCS). Dr Wang has supervised research projects for both PhD and MSc students as their primary supervisor. He has also gained the recognition as the Fellow of the Higher Education Academy (FHEA) for his contribution at teaching and training both undergraduates and postgraduates.

报告内容：

Prostate cancer (PCa) is the main leading cause of cancer death in men worldwide and preferentially metastasize into the skeleton. Once skeletal metastases have been established, the disease is considered to be incurable. A subpopulation of PCa cells (metastasis initiating cells) have been shown to have the potential to leave the primary site, survive in the circulation and home into the bone, where they eventually form bone metastases. P2X4 receptor (P2X4R), an ATP binding purinergic receptor, was found to be significantly up-regulated at transcription level in these metastasis initiating cells. Therefore in this project, we will test the hypothesis that P2X4R has a pro-tumour role. To test this hypothesis, P2X4R was pharmaceutically inhibited using two specific P2X4R antagonists (PSB-12062 at 1.5μM and 5-BDBD at 1.0μM) in two PCa cell lines: the osteolytic type PC3 and osteoblastic type C4-2B4. Examined and compared to vehicle controls using the CyQUANT® NF Cell proliferation assay, the proliferation of PCa cells was found to be significantly decreased under the treatment of P2X4R antagonists (by 48.69% and 67.92% in PC3 treated with PSB-12062 and 5-BDBD respectively; by 69.03% and 78.01% in treated C4 2B4 cells). Data generated using AlamarBlue cell viability assay suggested that there is no significant change in the viability of PC3 cells after treatment of P2X4R antagonists but the viability of C4-2B4 cells decrease dramatically (by 56.39% and 36.80% treated with PSB-12062 and 5-BDBD respectively). Furthermore, inhibition of P2X4R in PC3 cells led to significant decrease in ability of migration (>25%) and invasion (>50%), examined using scratch test and Transwell® assays, respectively. Finally, inhibiting P2X4R significantly impaired the viability of P2X7R (another ATP receptor) knockout PC3 cells but not wildtype cells, suggesting P2X4R functions in coordination with P2X7R in PCa cells. In summary, our data suggests that P2X4R plays a vital role in PCa cell biology and warrants further studies to reveal the potential of targeting P2X4R to treat PCa.