Stimulation of growth of a colon cancer cell line by gastrin

1986 ◽  
Vol 251 (5) ◽  
pp. G597-G601 ◽  
Author(s):  
C. J. Kusyk ◽  
N. O. McNiel ◽  
L. R. Johnson

A relation between duodenal myoelectric and motor activity and alkaline secretion has been investigated in conscious dogs under basal conditions and following vagal excitation with and without pretreatment with atropine or indomethacin. It was found that duodenal alkaline secretion shows typical periodicity in phase with the myoelectric or motor activity of the duodenum, reaching a peak during phase III and a nadir during phase I of the migrating motor complex (MMC). Sham feeding interrupted the motor and secretory MMC cycle and caused a prolonged increase in duodenal myoelectric or motor activity as well as a sudden and marked rise in duodenal alkaline secretion accompanied by a significant elevation in plasma gastrin and pancreatic polypeptide. Atropine and indomethacin abolished the motor and secretory duodenal cycles and reduced basal alkaline secretion significantly. Atropine abolished, whereas indomethacin increased duodenal myoelectric or motor activity during basal conditions and after vagal stimulation. Neither atropine nor indomethacin abolished sham feeding-induced duodenal alkaline secretion. We conclude that duodenal alkaline secretion fluctuates cyclically in phase with duodenal motility, vagal excitation results in a potent stimulation of duodenal motor and secretory activity, and the mechanism of vagally induced duodenal alkaline secretion is only partly cholinergic and does not involve endogenous generation of prostaglandins.

1986 ◽  
Vol 251 (5) ◽  
pp. G591-G596 ◽  
Author(s):  
S. J. Konturek ◽  
P. Thor

A relation between duodenal myoelectric and motor activity and alkaline secretion has been investigated in conscious dogs under basal conditions and following vagal excitation with and without pretreatment with atropine or indomethacin. It was found that duodenal alkaline secretion shows typical periodicity in phase with the myoelectric or motor activity of the duodenum, reaching a peak during phase III and a nadir during phase I of the migrating motor complex (MMC). Sham feeding interrupted the motor and secretory MMC cycle and caused a prolonged increase in duodenal myoelectric or motor activity as well as a sudden and marked rise in duodenal alkaline secretion accompanied by a significant elevation in plasma gastrin and pancreatic polypeptide. Atropine and indomethacin abolished the motor and secretory duodenal cycles and reduced basal alkaline secretion significantly. Atropine abolished, whereas indomethacin increased duodenal myoelectric or motor activity during basal conditions and after vagal stimulation. Neither atropine nor indomethacin abolished sham feeding-induced duodenal alkaline secretion. We conclude that duodenal alkaline secretion fluctuates cyclically in phase with duodenal motility, vagal excitation results in a potent stimulation of duodenal motor and secretory activity, and the mechanism of vagally induced duodenal alkaline secretion is only partly cholinergic and does not involve endogenous generation of prostaglandins.


2008 ◽  
Vol 294 (5) ◽  
pp. G1210-G1218 ◽  
Author(s):  
Koji Ataka ◽  
Akio Inui ◽  
Akihiro Asakawa ◽  
Ikuo Kato ◽  
Mineko Fujimiya

Obestatin is a novel peptide encoded by the ghrelin precursor gene; however, its effects on gastrointestinal motility remain controversial. Here we have examined the effects of obestatin on fed and fasted motor activities in the stomach and duodenum of freely moving conscious rats. We examined the effects of intravenous (IV) injection of obestatin on the percentage motor index (%MI) and phase III-like contractions in the antrum and duodenum. The brain mechanism mediating the action of obestatin on gastroduodenal motility and the involvement of vagal afferent pathway were also examined. Between 30 and 90 min after IV injection, obestatin decreased the %MI in the antrum and prolonged the time taken to return to fasted motility in the duodenum in fed rats given 3 g of chow after 18 h of fasting. Immunohistochemical analysis demonstrated that corticotropin-releasing factor- and urocortin-2-containing neurons in the paraventricular nucleus in the hypothalamus were activated by IV injection of obestatin. Intracerebroventricular injection of CRF type 1 and type 2 receptor antagonists prevented the effects of obestatin on gastroduodenal motility. Capsaicin treatment blocked the effects of obestatin on duodenal motility but not on antral motility. Obestatin failed to antagonize ghrelin-induced stimulation of gastroduodenal motility. These results suggest that, in the fed state, obestatin inhibits motor activity in the antrum and duodenum and that CRF type 1 and type 2 receptors in the brain might be involved in these effects of obestatin on gastroduodenal motility.


1987 ◽  
Vol 252 (6) ◽  
pp. G742-G747 ◽  
Author(s):  
S. J. Konturek ◽  
P. Thor ◽  
J. Bilski ◽  
J. Tasler ◽  
M. Cieszkowski

Alkaline secretion measured under basal conditions in the intact stomach of conscious dogs averaged 47 mumol/30 min and was about twice lower than that recorded in the proximal (approximately 7 cm long) portion of the duodenum. Vagal excitation elicited by sham feeding and insulin resulted in a marked stimulation of alkaline secretion both from the stomach and the duodenum. Atropine significantly reduced gastric and duodenal alkaline secretion under basal state. It abolished gastric and diminished duodenal alkaline response to sham feeding and insulin hypoglycemia, while propranolol was without significant influence. Indomethacin reduced by approximately 75% basal duodenal alkaline secretion but did not prevent the increment in alkaline response to vagal stimulation. We postulate the existence of the cephalic phase of gastroduodenal alkaline secretion, which seems to be cholinergically dependent in the stomach and partly of noncholinergic and nonadrenergic character but prostaglandin dependent in the duodenum.


1986 ◽  
Vol 250 (5) ◽  
pp. G570-G574
Author(s):  
S. J. Konturek ◽  
P. J. Thor ◽  
J. Bilski ◽  
W. Bielanski ◽  
J. Laskiewicz

A relationship between duodenal myoelectric or motor activity and exocrine pancreatic secretion as well as plasma gut hormone levels has been investigated in fasted dogs, fed dogs, and dogs that were stimulated with exogenous gut hormones. Pancreatic secretion showed typical periodicity in phase with the myoelectric or motor activity of the duodenum. Fasting pancreatic bicarbonate and protein secretion reached peaks during phase III of the interdigestive migrating motor complex (MMC) cycle that were significantly larger than nadir levels occurring during phase I of the cycle. These fasting bicarbonate and protein peaks reached, respectively, approximately 9 and 30% of the highest postprandial outputs and 4 and 14% of the maximal secretory capacity elicited by secretin or CCK. They were accompanied by a significant rise in plasma motilin, gastrin, and pancreatic polypeptide (PP), but only exogenous motilin given in physiological dose induced motility pattern and pancreatic secretion similar to those observed during phase III. Feeding interrupted both motor and secretory MMC cycle, increased the pancreatic secretion to approximately 40-60% of the maximal secretory capacity, and was accompanied by increments in plasma gastrin, cholecystokinin (CCK), secretin, and PP. None of these hormones applied alone in physiological dose was capable of reproducing the postprandial inhibition of MMC cycles. We conclude that the pancreatic secretion in fasted dogs fluctuates periodically in phase with duodenal motility, but the phase III peak secretory outputs represent only minute fractions of the maximal secretory capacity and can therefore be ignored in regular testing of pancreatic secretion.


Author(s):  
Yuan Feng ◽  
Xinran Liu ◽  
Yueqing Han ◽  
Mantian Chen ◽  
Lin Zhang ◽  
...  

Background & Objective: Nowadays, the interaction between natural products and microRNAs provides a promising field for exploring the chemo preventive agents for various cancers.As a member of microRNAs, the expression of let-7f-5p is universally down regulated in colorectal cancer (CRC). The present study aimed to uncover the function of let-7f-5p in the proliferation of human colon cancer cell line Caco2 and explored chemo preventive agents from natural resources that can prevent the development of CRC. Methods: Herein, Caco2 cells were transfected with let-7f-5p mimic and inhibitor to manipulate let-7f-5p levels, and the expression of let-7f-5p wasper formed by RT‑qPCR. Next, we determined how let-7f-5p regulates Caco2 cell proliferation by using MTT, wound-healing, cell cycle,and colony formation assays.Besides, to further understand the effect of let-7f-5p, we evaluated the protein level of AMER3 and SLC9A9 by using western blotting assays. Results: The results showed a suppressive function of let-7f-5p on Caco2 cell proliferation and then put forward a triterpenoid (rotundic acid, RA) which significant antagonized the effect of cell proliferation, restitution after wounding,and colony formation caused by let-7f-5p. Moreover, the western blot results further indicated that the inhibitory effect of RA might be due to its suppressive role in let-7f-5p-targeted AMER3 and SLC9A9 regulation. Conclusion: Our validation study results confirmed that let-7f-5p was a potent tumor suppressor gene of Caco2 cell proliferation,and RA showed as a regulator of the effect oflet-7f-5p on cell proliferation and then could be a potential chemo preventive agent for CRC treatment.


2018 ◽  
Vol 18 (8) ◽  
pp. 1148-1155 ◽  
Author(s):  
Leili Asadi ◽  
Sakine Shirvalilou ◽  
Sepideh Khoee ◽  
Samideh Khoei

Background: Despite the development of conventional therapies including surgery, radiotherapy, chemotherapy and hyperthermia, the prognosis remains very poor. Recently, integration of conventional therapy and multifunctional nanoparticles have attracted a lot of attention because it produces a synergistic effect and better diagnostic and therapeutic efficiency. Objective: This study aimed to investigate the uptake and cytotoxic effects of Polycaprolactone (PCL)/chitosan (CHI)-coated Superparamagnetic Iron Oxide Nano-Graphene Oxide (SPION-NGO) as a carrier of 5-fluorouracil (5-Fu) and Radiofrequency (RF) hyperthermia using an Alternate Magnetic Field (AMF) with 13.56 MHz frequency on the proliferation capacity level of CT26 colon cancer cell line in a monolayer culture. Method: The release of the newly synthesised 5-Fu-loaded PCL/CHI-SPION-NGO was measured in Phosphate Buffered Saline (PBS) using the dialysis bag method. The cellular uptake of 5-Fu-loaded PCL/CHI-SPIONNGO was measured using Atomic Absorption Spectroscopy (AAS). The cytotoxic effects of 5-Fu, 5-Fu- PCL/CHI-SPION-NGO and PCL/CHI-SPION-NGO with and without RF hyperthermia were determined using the colony formation assay. Results: Particle size and zeta potential of 5-Fu-PCL/CHI-SPION-NGO and PCL/CHI-SPION-NGO were 61.2 nm and -1.87 mV and 43.4 nm and -10.19 mV, respectively. Spectroscopy results demonstrated that the cellular uptake of 5-Fu-PCL/CHI-SPION-NGO increased with elevated nanostructure concentrations. The results revealed that the proliferation capacity of the cells decreased with 5-Fu or 5-Fu-PCL/CHI-SPION-NGO in combination with RF hyperthermia. Furthermore, extent of reduction in colony number following treatment with 5-Fu-PCL/CHI-SPION-NGO in combination with AMF was significantly more than 5-Fu + hyperthermia. Conclusion: Therefore, PCL/CHI-SPION-NGO can deliver 5-Fu more efficiently into the CT26 cells.


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