19-peptide, a fragment of tumstatin, inhibits the growth of poorly differentiated gastric carcinoma cells in vitro and in vivo.
OBJECTIVE
This study investigated whether 19-peptide, a fragment of tumstatin, inhibited the growth of gastric tumor cells in vitro and in vivo.


METHODS
19-peptide was expressed in bacteria and purified with Sephadex G-15. SGC7901 gastric carcinoma cells and human umbilical-vein endothelial cells (HUVECs) were exposed to 19-peptide in vitro, and their viability was evaluated by biochemical and histopathological analysis. In vivo, pieces of solid tumor derived from SGC7901 cells were inoculated into the gastric serosa of 36 nude mice, with a biological glue to hold them in place. Twenty-eight days after injection of 19-peptide, the mice were killed. The tumors were measured and examined by western blotting, histopathology, and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assay.


RESULTS
19-peptide induced apoptosis of many SGC7901 cells but few HUVECs in vitro. In vivo, after the application of 19-peptide, significant tumor cell apoptosis was observed in the center of the tumors, tumor volume was reduced significantly (P < 0.001), and the invasion and migration of cancer cells was reduced. PTEN was increased in the treatment group and phospho-Akt (pAkt) was decreased in the control group.


CONCLUSIONS
These results suggest that 19-peptide inhibits the growth and metastases of poorly differentiated gastric carcinoma cells, primarily by inducing apoptosis. The apoptotic mechanism could be related to anoikis and the PTEN/Akt pathway.
He
Yan
Y
Department of Pathology, Harbin Medical University, Harbin, China.
Jiang
Yang
Y
Li
Ying-Jie
YJ
Liu
Xing-Han
XH
Zhang
Lei
L
Liu
Li-Juan
LJ
Shi
Hang
H
Li
Hui-Ning
HN
Ma
Yong-Cu
YC
Jin
Xiao-Ming
XM
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001324:Autoantigens / Q000494:pharmacology*; D015153:Blotting, Western; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D024141:Collagen Type IV / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D001324:Autoantigens; D024141:Collagen Type IV; D010446:Peptide Fragments; C057112:type IV collagen alpha3 chain; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human