title: Octreotide inhibits the proliferation of gastric cancer cells through P300-HAT activity and the interaction of ZAC and P300.
abstract: Somatostatin (SST) exhibits a wide range of physiological functions, including the regulation of tumor cell growth. Octreotide (OCT) is a synthetic analogue of SST that can be used to slow gastrointestinal bleeding, inhibit the release of growth hormone and impede gastrointestinal tumor growth. The aim of the present study was to investigate the molecular mechanism of OCT underlying the inhibition of gastric cancer cell proliferation. Proteins of interest were detected using western blotting, and the zinc finger protein (ZAC)-P300 complex was quantified using co-immunoprecipitation. P300-histone acetyltransferase (P300-HAT) activity was determined spectrophotometrically. The results showed that OCT decreased the phosphorylation of Akt which caused the level of ZAC to increase. In turn, the interaction between ZAC and P300 increased the activity of P300-HAT; ultimately, the phosphorylation of serine 10 in histone H3 (pS10-H3) was decreased and the acetylation of lysine 14 in histone H3 (acK14-H3) was increased. These results suggest that OCT attenuates SGC-7901 cell proliferation by enhancing P300-HAT activity through the interaction of ZAC and P300, causing a reduction in pS10-H3 and an increase in acK14-H3. These findings provide insight for future research on OCT and further demonstrate the potential of OCT to be used as a therapeutic agent for gastric cancer.
authors.affiliation: Department of Histology and Embryology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Histology and Embryology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Histology and Embryology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Yurong
authors.initials: Y
authors.lastname: Chai
authors.affiliation: Department of Histology and Embryology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Liyang
authors.initials: L
authors.lastname: Zou
authors.affiliation: Department of Psychology and Neuroscience, Faculty of Science, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada.
authors.forename: Matthew
authors.initials: M
authors.lastname: Chedrawe
authors.affiliation: Department of Histology and Embryology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
mesh_terms: D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050881:E1A-Associated p300 Protein / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D015282:Octreotide / Q000008:administration & dosage*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D013004:Somatostatin / Q000008:administration & dosage; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; C106464:PLAGL1 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D013004:Somatostatin; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D015282:Octreotide