oxytocin and Pancreatic-Neoplasms

Oxytocin (OXT) and its receptor (OXTR) is associated with cancer. The present study was to investigate the correlation between the genetic expression alterations of OXT and OXTR and the outcomes in patients with pancreatic cancer (PC).. Information regarding OXT and OXTR genetic alterations and changes in gene expression were retrieved from the Cancer Genome Atlas (TCGA) databases and analyzed using the cBioPortal online tool. We assessed the correlation of overall survival and disease/progression-free months to either OXT or OXTR genetic alterations and changes in gene expression using Kaplan-Meier and Cox regression analyses. Quantitative PCR (qPCR) was conducted to assess the mRNA expression levels of OXT and OXTR in human PC cell lines.. Five percent of PC cases showed mRNA upregulation in the OXT gene. These PC cases also showed genetic alterations and changes in gene expression of OXTR. The median months of survival and disease-free survival were lower for PC cases with genetic alterations and changes in gene expression in the OXT and OXTR genes as compared to those without such alterations. qPCR data showed that OXT and OXTR mRNA expression were 1-fold and 10-fold higher, respectively in PANC-1 cell lines as compared to L3.6pl cell lines in direct negative correlation with responsiveness to gemcitabine.. These data suggest that OXT and OXTR may potentially be important in PC progression, chemoresistance, and patient survival, and potentially could have prognostic and therapeutic implications in a subset of PC patients.

Topics: Cell Line, Tumor; Databases, Genetic; Disease-Free Survival; Drug Resistance, Neoplasm; Gene Expression; Humans; Kaplan-Meier Estimate; Mutation; Oxytocin; Pancreatic Neoplasms; Progression-Free Survival; Proportional Hazards Models; Receptors, Oxytocin; RNA, Messenger; Survival Rate; Up-Regulation

Receptor antagonists were used to determine which receptor mediates the effect of arginine vasopressin (AVP) and oxytocin (OT) on glucagon release from hamster glucagonoma In-R1-G9 cells. Both AVP (10(-9)-10(-6) M) and OT (10(-8)-10(-5) M) increased glucagon release from In-R1-G9 cells in a concentration-dependent manner and AVP was approximately 30-fold more potent than OT in this aspect. The antagonists with potent V1b receptor blocking activity, CL-4-84 (10(-9)-10(-6) M), dP[Tyr(Me)2]AVP and AO-2-44 (10(-8)-10(-6) M), antagonized the effect of both AVP and OT in a concentration-dependent manner. Other receptor antagonists at 10(-6) M failed to block the effect of AVP and OT; these included a highly selective OT-receptor antagonist, L-366,948 and a V1a/V2 receptor antagonist WK-3-6. However, these antagonists at higher concentrations (10(-5) and 10(-4) M) caused inhibition of AVP- and OT-induced glucagon release. The order of antagonistic potency was estimated as CL-4-84 approximately = dP[Tyr(Me)2]AVP approximately = AO-2-44 > WK 3-6 > L366,948. d[D-3-Pal]VP (10(-8)-10(-5) M), a V1b receptor agonist, also increased glucagon release in a concentration-dependent manner, which was antagonized by dP[Tyr(Me)2]AVP (10(-8)-10(-6) M) and CL-4-84 (10(-9)-10(-6) M), but not by WK-3-6 (10(-6) M) or L-366,948 (10(-6) M). Therefore, the stimulatory effects of both OT and AVP on glucagon release may be mediated by V1b receptors, but not by V1a, V2, or OT receptors.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Cricetinae; Dose-Response Relationship, Drug; Glucagon; Glucagonoma; Hormone Antagonists; Islets of Langerhans; Oxytocin; Pancreatic Neoplasms; Peptides, Cyclic; Receptors, Oxytocin; Receptors, Vasopressin; Renal Agents; Tumor Cells, Cultured

To study the mechanisms underlying oxytocin (Oxy)-induced insulin release.. In a clonal pancreatic beta-cell line, RINm5F cells.. Oxy increased insulin release and [Ca2+]i in a concentration-dependent manner. Oxy-induced insulin release was not altered by pretreatment with pertussis toxin (PT). U-73122 (2-8 mumol.L-1), a phospholipase C (PLC) inhibitor, concentration-dependently inhibited Oxy-induced increases in [Ca2+]i with IC50 value of 2.8 +/- 0.2 mumol.L-1. In addition, U-73122 diminished the Oxy-induced increase in intracellular concentration of inositol 1, 4, 5-triphosphate (IP3). U-73122 at 8 mumol.L-1 totally abolished the Oxy-induced increases in [Ca2+]i and IP3; however it reduced the Oxy-induced increase in insulin release only by 36% and 63% in the monolayer and suspended cell preparations, respectively.. Oxy increases insulin release through both PLC and non-PLC mediated signal transduction mechanisms.

Topics: Animals; Calcium; Estrenes; Inositol Phosphates; Insulin; Insulinoma; Oxytocin; Pancreatic Neoplasms; Phosphodiesterase Inhibitors; Pyrrolidinones; Rats; Tumor Cells, Cultured; Type C Phospholipases

Topics: Adenocarcinoma; Animals; Carcinoma, Bronchogenic; Choriocarcinoma; Culture Media; Diuresis; Female; In Vitro Techniques; Liver; Liver Neoplasms; Lung Neoplasms; Neoplasm Metastasis; Oxytocin; Pancreatic Neoplasms; Pregnancy; Rats; Recurrence; Uterine Neoplasms; Vasopressins

Topics: Adenocarcinoma; Animals; Biological Assay; Carcinoma, Bronchogenic; Chickens; Humans; Hyponatremia; Lung Neoplasms; Male; Methods; Middle Aged; Neoplasm Metastasis; Neoplasms, Multiple Primary; Osmolar Concentration; Oxytocin; Pancreatic Neoplasms; Pneumonectomy; Rabbits; Radioimmunoassay; Rats; Vasopressins