Nodal Enhances Perineural Invasion in Pancreatic Cancer by Promoting Tumor-Nerve Convergence.

Perineural invasion (PNI) is a typical feature of pancreatic ductal adenocarcinoma (PDAC), which occurs in most cases. The embryonic protein Nodal plays a critical role in embryonic neural development and is overexpressed in human pancreatic cancer. In this study, we explored the contribution of Nodal to pancreatic cancer PNI and progression.

HIF-1alpha links beta-adrenoceptor agonists and pancreatic cancer cells under normoxic condition.

Aim: To examine whether beta-adrenoceptor (beta-AR) agonists can induce hypoxia-inducible factor (HIF)-1alpha accumulation which then up-regulate the expression of its target genes in pancreatic cancer cells at normoxia, and to further elucidate the mechanism involved.

Methods: Pulse-chase assay, RT-PCR, and Western blot were employed to detect the effects of beta-AR agonists and antagonists, siRNA as well as several inhibitors of signal transduction pathways on MIA PaCa2 and BxPC-3 pancreatic cancer cells.

Results: Treatment of pancreatic cancer cell lines with beta-AR agonists led to accumulation of HIF-1alpha and then up-regulated expression of its target genes independently of oxygen levels.

Inhibition of pancreatic cancer cell proliferation by propranolol occurs through apoptosis induction: the study of beta-adrenoceptor antagonist's anticancer effect in pancreatic cancer cell.

Objectives: Propranolol inhibited pancreatic cancer cell proliferation by blocking signaling through the beta-adrenoceptor. We hypothesized that propranolol may suppress pancreatic cancer cell growth through induction of apoptosis.

Methods: The beta-adrenoceptor antagonist propranolol, beta1-adrenoceptor antagonist metoprolol, and beta2-adrenoceptor antagonist butoxamine were used to induce apoptosis in PC-2 cells.

Stimulation of dorsal root ganglion neurons activity by pancreatic cancer cell lines.

Stimulation of mice dorsal root ganglion neurons (DRGNs) activity by human pancreatic cancer (PanCa) cell line Mia PaCa-2 and its potential molecule mechanism has been investaged. DRGNs were cultured alone or along with the MIA PaCa-2. The effects of MIA PaCa-2 to DRGNs were determined by neurofilament (NF) immunocytochemical and Nissl staining.

Effects of alpha-adrenoreceptor antagonists on apoptosis and proliferation of pancreatic cancer cells in vitro.

Aim: To discuss the expression of alpha-adrenoreceptors in pancreatic cancer cell lines PC-2 and PC-3 and the effects of alpha1- and alpha2-adrenoreceptor antagonists, yohimbine and urapidil hydrochloride, on the cell lines in vitro.

Methods: We cultured the human ductal pancreatic adenocarcinoma cell lines PC-2 and PC-3 and analyzed the mRNA expression of alpha1- and alpha2-adrenergic receptors by reverse transcription polymerase chain reaction (RT-PCR). The effects of yohimbine and urapidil hydrochloride on cell proliferation were assessed by 3-(4,5-dimethylthiasol-2-yl)-2,4,-diphenyltetrazolium bromide (MTT) assay.

[Construction of the recombinant adenovirus mediated shRNA to silence PTN in pancreatic carcinoma and the effect of DRGn on neurite in vitro].

Aim: To construct the replication-incompetent recombinant adenovirus mediated shRNA to inhibit the neurite growth-promoting factor (Pleiotrophin, PTN) in pancreatic carcinoma and to study the inhibitory effect of shRNA-PTN recombinant adenoviruses on the neurite's growth of dorsal root ganglion neurons (DRGn).

Methods: Four pairs of complementary single-stranded oligonucleotides (ss oligo) were designed and synthesized and then they were annealed to create a double-stranded oligonucleotide (ds oligo). The ds oligos were cloned into pENTR/U6 vector to produce the shuttle plasmid pENTR/U6-shRNA, which was transduced into pancreatic carcinoma cells by liposome after sequencing.