Activation of the P2Y(1) receptor induces apoptosis and inhibits proliferation of prostate cancer cells

作者：Wei, Qiang; Costanzi, Stefano; Liu, Qiu Zhen; Gao, Zhan Guo; Jacobson, Kenneth A^*

来源：Biochemical Pharmacology, 2011, 82(4): 418-425.

DOI：10.1016/j.bcp.2011.05.013

• Prostate cancer
• P2Y(1) receptor
• Apoptosis
• Nucleotide
• GPCR

G protein-coupled receptors, the largest cell surface receptor family, have emerged as critical players in cell death and survival. High gene expression level of the G(q)-coupled P2Y(1) nucleotide receptor in PC-3 prostate cancer cells was demonstrated using real-time quantitative PCR and confirmed by Western blotting and confocal laser scanning microscopy. A selective P2Y(1) receptor agonist, the ADP analogue MRS2365, concentration-dependently induced intracellular calcium mobilization (EC50 5.28 nM), which was diminished by P2Y(1) receptor-selective antagonist MRS2500. P2Y(1) receptor activation by MRS2365 induced apoptosis in assays of Caspase-3. LDH release, and annexin-V staining. The pro-apoptotic effect of MRS2365 was blocked by MRS2500, P2Y(1) siRNA, and an inhibitor of the MAP kinase pathway PD98059. MRS2365 significantly inhibited the proliferation of PC-3 cells, examined using a MTT assay. Thus, activation of the P2Y(1) receptor induced cell death and inhibited growth of human prostatic carcinoma PC-3 cells. Activation of the P2Y(1) receptor should be a novel and promising therapeutic strategy for prostate cancer. Published by Elsevier Inc.

• 出版日期2011-8-15
• 单位南方医科大学